![Polypeptide forming an alpha helix, with hydrogen bonds in magenta](https://upload.wikimedia.org/wikipedia/commons/c/ca/Polypeptide_forming_an_alpha_helix%2C_with_hydrogen_bonds_in_magenta.gif)
The alpha helix (α-helix) is a common
motif in the
secondary structure
Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...
of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s and is a
right hand
In human biology, handedness is an individual's preferential use of one hand, known as the dominant hand, due to it being stronger, faster or more dextrous. The other hand, comparatively often the weaker, less dextrous or simply less subjecti ...
-
helix
A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined helices, ...
conformation in which every backbone
N−H group
hydrogen bonds
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...
to the backbone
C=O group of the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
located four
residues earlier along the protein sequence.
The alpha helix is also called a classic Pauling–Corey–Branson α-helix. The name 3.6
13-helix is also used for this type of helix, denoting the average number of residues per helical turn, with 13 atoms being involved in the ring formed by the hydrogen bond.
Among types of local structure in proteins, the α-helix is the most extreme and the most predictable from sequence, as well as the most prevalent.
Discovery
In the early 1930s,
William Astbury
William Thomas Astbury FRS (25 February 1898 – 4 June 1961) was an English physicist and molecular biologist who made pioneering X-ray diffraction studies of biological molecules. His work on keratin provided the foundation for Linus Pauling ...
showed that there were drastic changes in the
X-ray
An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...
fiber diffraction
Fiber diffraction is a subarea of scattering, an area in which molecular structure is determined from scattering data (usually of X-rays, electrons or neutrons). In fiber diffraction the scattering pattern does not change, as the sample is rotat ...
of moist wool or hair fibers upon significant stretching. The data suggested that the unstretched fibers had a coiled molecular structure with a characteristic repeat of ≈.
Astbury initially proposed a linked-chain structure for the fibers. He later joined other researchers (notably the American chemist
Maurice Huggins) in proposing that:
* the unstretched protein molecules formed a helix (which he called the α-form)
* the stretching caused the helix to uncoil, forming an extended state (which he called the β-form).
Although incorrect in their details, Astbury's models of these forms were correct in essence and correspond to modern elements of
secondary structure
Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...
, the α-helix and the
β-strand
The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...
(Astbury's nomenclature was kept), which were developed by
Linus Pauling
Linus Carl Pauling (; February 28, 1901August 19, 1994) was an American chemist, biochemist, chemical engineer, peace activist, author, and educator. He published more than 1,200 papers and books, of which about 850 dealt with scientific top ...
,
Robert Corey
Robert Brainard Corey (August 19, 1897 – April 23, 1971) was an American biochemist, mostly known for his role in discovery of the α-helix and the β-sheet with Linus Pauling. Also working with Pauling was Herman Branson. Their discoveries w ...
and
Herman Branson
Herman Russell Branson (August 14, 1914 – June 7, 1995) was an American physicist, chemist, best known for his research on the alpha helix protein structure, and was also the president of two colleges. He received a fellowship from the Rosenwal ...
in 1951 (see below); that paper showed both right- and left-handed helices, although in 1960 the crystal structure of myoglobin showed that the right-handed form is the common one.
Hans Neurath
Hans Neurath (October 29, 1909 – April 2002) was a biochemist, a leader in protein chemistry, and the founding chairman of the Department of Biochemistry at the University of Washington in Seattle. He was born in Vienna, Austria and received ...
was the first to show that Astbury's models could not be correct in detail, because they involved clashes of atoms. Neurath's paper and Astbury's data inspired
H. S. Taylor,
Maurice Huggins and
Bragg Bragg may refer to:
Places
*Bragg City, Missouri, United States
*Bragg, Texas, a ghost town, United States
*Bragg, West Virginia, an unincorporated community, United States
*Electoral district of Bragg, a state electoral district in South Australia ...
and collaborators to propose models of
keratin
Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ho ...
that somewhat resemble the modern α-helix.
Two key developments in the modeling of the modern α-helix were: the correct bond geometry, thanks to the
crystal structure determinations of
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s and
peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A ...
s and Pauling's prediction of ''planar''
peptide bond
In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein cha ...
s; and his relinquishing of the assumption of an integral number of residues per turn of the helix. The pivotal moment came in the early spring of 1948, when Pauling caught a cold and went to bed. Being bored, he drew a polypeptide chain of roughly correct dimensions on a strip of paper and folded it into a helix, being careful to maintain the planar peptide bonds. After a few attempts, he produced a model with physically plausible hydrogen bonds. Pauling then worked with Corey and Branson to confirm his model before publication. In 1954, Pauling was awarded his first Nobel Prize "for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances" (such as proteins), prominently including the structure of the α-helix.
Structure
Geometry and hydrogen bonding
The amino acids in an α-helix are arranged in a right-handed
helical
Helical may refer to:
* Helix, the mathematical concept for the shape
* Helical engine, a proposed spacecraft propulsion drive
* Helical spring, a coilspring
* Helical plc, a British property company, once a maker of steel bar stock
* Helicoil
A t ...
structure where each amino acid residue corresponds to a 100° turn in the helix (i.e., the helix has 3.6 residues per turn), and a translation of along the helical axis. Dunitz describes how Pauling's first article on the theme in fact shows a left-handed helix, the enantiomer of the true structure. Short pieces of left-handed helix sometimes occur with a large content of achiral
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...
amino acids, but are unfavorable for the other normal, biological
-amino acids. The pitch of the alpha-helix (the vertical distance between consecutive turns of the helix) is , which is the product of 1.5 and 3.6. What is most important is that the
N-H group of an amino acid forms a
hydrogen bond
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...
with the
C=O group of the amino acid ''four'' residues earlier; this repeated ''i'' + 4 → ''i'' hydrogen bonding is the most prominent characteristic of an α-helix. Official international nomenclature
specifies two ways of defining α-helices, rule 6.2 in terms of repeating ''φ'', ''ψ'' torsion angles (see below) and rule 6.3 in terms of the combined pattern of pitch and hydrogen bonding. The α-helices can be identified in protein structure using several computational methods, one of which is
DSSP (Define
Secondary Structure
Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...
of Protein).
Similar structures include the
310 helix (''i'' + 3 → ''i'' hydrogen bonding) and the
π-helix (''i'' + 5 → ''i'' hydrogen bonding). The α-helix can be described as a 3.6
13 helix, since the ''i'' + 4 spacing adds three more atoms to the H-bonded loop compared to the tighter 3
10 helix, and on average, 3.6 amino acids are involved in one ring of α-helix. The subscripts refer to the number of atoms (including the hydrogen) in the closed loop formed by the hydrogen bond.
Residues in α-helices typically adopt backbone (''φ'', ''ψ'')
dihedral angle
A dihedral angle is the angle between two intersecting planes or half-planes. In chemistry, it is the clockwise angle between half-planes through two sets of three atoms, having two atoms in common. In solid geometry, it is defined as the uni ...
s around (−60°, −45°), as shown in the image at right. In more general terms, they adopt dihedral angles such that the ''ψ'' dihedral angle of one residue and the ''φ'' dihedral angle of the ''next'' residue sum to roughly −105°. As a consequence, α-helical dihedral angles, in general, fall on a diagonal stripe on the
Ramachandran diagram
In biochemistry, a Ramachandran plot (also known as a Rama plot, a Ramachandran diagram or a ,ψplot), originally developed in 1963 by G. N. Ramachandran, C. Ramakrishnan, and V. Sasisekharan, is a way to visualize energetically allowed regio ...
(of slope −1), ranging from (−90°, −15°) to (−70°, −35°). For comparison, the sum of the dihedral angles for a 3
10 helix is roughly −75°, whereas that for the π-helix is roughly −130°. The general formula for the rotation angle ''Ω'' per residue of any polypeptide helix with ''trans'' isomers is given by the equation
:
The α-helix is tightly packed; there is almost no free space within the helix. The amino-acid side-chains are on the outside of the helix, and point roughly "downward" (i.e., toward the N-terminus), like the branches of an evergreen tree (
Christmas tree
A Christmas tree is a decorated tree, usually an evergreen conifer, such as a spruce, pine or fir, or an artificial tree of similar appearance, associated with the celebration of Christmas. The custom was further developed in early modern ...
effect). This directionality is sometimes used in preliminary, low-resolution electron-density maps to determine the direction of the protein backbone.
Stability
Helices observed in proteins can range from four to over forty residues long, but a typical helix contains about ten amino acids (about three turns). In general, short
polypeptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
s do not exhibit much α-helical structure in solution, since the
entropic
Entropy is a scientific concept, as well as a measurable physical property, that is most commonly associated with a state of disorder, randomness, or uncertainty. The term and the concept are used in diverse fields, from classical thermodynam ...
cost associated with the folding of the polypeptide chain is not compensated for by a sufficient amount of stabilizing interactions. In general, the backbone
hydrogen bond
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...
s of α-helices are considered slightly weaker than those found in
β-sheets
The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...
, and are readily attacked by the ambient water molecules. However, in more hydrophobic environments such as the
plasma membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
, or in the presence of co-solvents such as
trifluoroethanol
2,2,2-Trifluoroethanol is the organic compound with the formula CF3CH2OH. Also known as TFE or trifluoroethyl alcohol, this colourless, water-miscible liquid has a smell reminiscent of ethanol. Due to the electronegativity of the trifluoromethyl ...
(TFE), or isolated from solvent in the gas phase, oligopeptides readily adopt stable α-helical structure. Furthermore, crosslinks can be incorporated into peptides to conformationally stabilize helical folds. Crosslinks stabilize the helical state by entropically destabilizing the unfolded state and by removing enthalpically stabilized "decoy" folds that compete with the fully helical state. It has been shown that α-helices are more stable, robust to mutations and designable than β-strands in natural proteins, and also in artificial designed proteins.
Visualization
The 3 most popular ways of visualizing the alpha-helical secondary structure of oligopeptide sequences are (1) a
helical wheel
A helical wheel is a type of plot or visual representation used to illustrate the properties of alpha helices in proteins.
The sequence of amino acids that make up a helical region of the protein's secondary structure are plotted in a rotating ...
, (2) a wenxiang diagram, and (3) a helical net. Each of these can be visualized with various software packages and web servers. To generate a small number of diagrams, Heliquest can be used for helical wheels, and NetWheels can be used for helical wheels and helical nets. To programmatically generate a large number of diagrams, helixvis can be used to draw helical wheels and wenxiang diagrams in the R and Python programming languages.
Experimental determination
Since the α-helix is defined by its hydrogen bonds and backbone conformation, the most detailed experimental evidence for α-helical structure comes from atomic-resolution
X-ray crystallography
X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
such as the example shown at right. It is clear that all the backbone carbonyl oxygens point downward (toward the C-terminus) but splay out slightly, and the H-bonds are approximately parallel to the helix axis. Protein structures from
NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fiel ...
also show helices well, with characteristic observations of
nuclear Overhauser effect The nuclear Overhauser effect (NOE) is the transfer of nuclear spin polarization from one population of spin-active nuclei (e.g. 1H, 13C, 15N etc.) to another via cross-relaxation. A phenomenological definition of the NOE in nuclear magnetic res ...
(NOE) couplings between atoms on adjacent helical turns. In some cases, the individual hydrogen bonds can be observed directly as a small scalar coupling in NMR.
There are several lower-resolution methods for assigning general helical structure. The
NMR
Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with ...
chemical shift
In nuclear magnetic resonance (NMR) spectroscopy, the chemical shift is the resonant frequency of an atomic nucleus relative to a standard in a magnetic field. Often the position and number of chemical shifts are diagnostic of the structure of ...
s (in particular of the C
α, C
β and C′) and
residual dipolar coupling The residual dipolar coupling between two spins in a molecule occurs if the molecules in solution exhibit a partial alignment leading to an incomplete averaging of spatially anisotropic dipolar couplings.
Partial molecular alignment leads to an in ...
s are often characteristic of helices. The far-UV (170–250 nm)
circular dichroism spectrum of helices is also idiosyncratic, exhibiting a pronounced double minimum at around 208 and 222 nm.
Infrared
Infrared (IR), sometimes called infrared light, is electromagnetic radiation (EMR) with wavelengths longer than those of visible light. It is therefore invisible to the human eye. IR is generally understood to encompass wavelengths from around ...
spectroscopy is rarely used, since the α-helical spectrum resembles that of a
random coil
In polymer chemistry, a random coil is a conformation of polymers where the monomer subunits are oriented randomly while still being bonded to adjacent units. It is not one specific shape, but a statistical distribution of shapes for all the ch ...
(although these might be discerned by, e.g.,
hydrogen-deuterium exchange). Finally, cryo
electron microscopy
An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
is now capable of discerning individual α-helices within a protein, although their assignment to residues is still an active area of research.
Long homopolymers of amino acids often form helices if soluble. Such long, isolated helices can also be detected by other methods, such as
dielectric relaxation
In electromagnetism, a dielectric (or dielectric medium) is an electrical insulator that can be polarised by an applied electric field. When a dielectric material is placed in an electric field, electric charges do not flow through the mater ...
,
flow birefringence
In biochemistry, flow birefringence is a hydrodynamic technique for measuring the rotational diffusion constants (or, equivalently, the rotational drag coefficients). The birefringence of a solution sandwiched between two concentric cylinders is ...
, and measurements of the
diffusion constant
Fick's laws of diffusion describe diffusion and were derived by Adolf Fick in 1855. They can be used to solve for the diffusion coefficient, . Fick's first law can be used to derive his second law which in turn is identical to the diffusion equ ...
. In stricter terms, these methods detect only the characteristic
prolate
A spheroid, also known as an ellipsoid of revolution or rotational ellipsoid, is a quadric surface obtained by rotating an ellipse about one of its principal axes; in other words, an ellipsoid with two equal semi-diameters. A spheroid has circ ...
(long cigar-like) hydrodynamic shape of a helix, or its large
dipole moment.
Amino-acid propensities
Different amino-acid sequences have different propensities for forming α-helical structure.
Methionine
Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
,
alanine
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side c ...
,
leucine
Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...
,
glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
, and
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
uncharged ("MALEK" in the
amino-acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ami ...
1-letter codes) all have especially high helix-forming propensities, whereas
proline
Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...
and
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...
have poor helix-forming propensities.
Proline
Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...
either breaks or kinks a helix, both because it cannot donate an amide
hydrogen bond
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...
(having no amide hydrogen), and also because its sidechain interferes sterically with the backbone of the preceding turn inside a helix, this forces a bend of about 30° in the helix's axis.
However, proline is often seen as the ''first'' residue of a helix, it is presumed due to its structural rigidity. At the other extreme,
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...
also tends to disrupt helices because its high conformational flexibility makes it entropically expensive to adopt the relatively constrained α-helical structure.
Table of standard amino acid alpha-helical propensities
Estimated differences in
free energy change, Δ(Δ''G''), estimated in
kcal/mol per residue in an α-helical configuration, relative to alanine arbitrarily set as zero. Higher numbers (more positive free energy changes) are less favoured. Significant deviations from these average numbers are possible, depending on the identities of the neighbouring residues.
:
Dipole moment
A helix has an overall
dipole moment due to the aggregate effect of the individual microdipoles from the
carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...
groups of the peptide bond pointing along the helix axis. The effects of this macrodipole are a matter of some controversy. α-helices often occur with the N-terminal end bound by a negatively charged group, sometimes an
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
side chain such as
glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
or
aspartate
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
, or sometimes a phosphate ion. Some regard the helix macrodipole as interacting electrostatically with such groups. Others feel that this is misleading and it is more realistic to say that the hydrogen bond potential of the free NH groups at the N-terminus of an α-helix can be satisfied by hydrogen bonding; this can also be regarded as set of interactions between local microdipoles such as .
Coiled coils
Coiled-coil α helices are highly stable forms in which two or more helices wrap around each other in a "supercoil" structure.
Coiled coil
A coiled coil is a structural motif in proteins in which 2–7
alpha-helices are coiled together like the strands of a rope. (Dimers and trimers are the most common types.) Many coiled coil-type proteins are involved in important biological fun ...
s contain a highly characteristic
sequence motif
In biology, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and usually assumed to be related to biological function of the macromolecule. For example, an ''N''-glycosylation site motif can be defined as ''As ...
known as a
heptad repeat
The heptad repeat is an example of a structural motif that consists of a repeating pattern of seven amino acids:
''a b c d e f g''
H P P H C P C
where H represents hydrophobic residues, C represents, typically, charged residues, and P repre ...
, in which the motif repeats itself every seven residues along the sequence (''amino acid'' residues, not DNA base-pairs). The first and especially the fourth residues (known as the ''a'' and ''d'' positions) are almost always
hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, th ...
; the fourth residue is typically
leucine
Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...
this gives rise to the name of the
structural motif
In a polymer, chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common Biomolecular structure#Tertiary structure, three-dimensional structure that appears in a variety of different, evolutionarily unrel ...
called a ''
leucine zipper
A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amin ...
'', which is a type of coiled-coil. These hydrophobic residues pack together in the interior of the helix bundle. In general, the fifth and seventh residues (the ''e'' and ''g'' positions) have opposing charges and form a salt bridge stabilized by
electrostatic
Electrostatics is a branch of physics that studies electric charges at rest (static electricity).
Since classical times, it has been known that some materials, such as amber, attract lightweight particles after rubbing. The Greek word for amber ...
interactions.
Fibrous protein
In molecular biology, fibrous proteins or scleroproteins are one of the three main classifications of protein structure (alongside globular and membrane proteins). Fibrous proteins are made up of elongated or fibrous polypeptide chains which fo ...
s such as
keratin
Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ho ...
or the "stalks" of
myosin
Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility.
The first myosin ...
or
kinesin
A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells.
Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzy ...
often adopt coiled-coil structures, as do several
dimerizing proteins. A pair of coiled-coils a four-
helix bundle A helix bundle is a small protein fold composed of several alpha helices that are usually nearly parallel or antiparallel to each other.
Three-helix bundles
Three-helix bundles are among the smallest and fastest known cooperatively folding struct ...
is a very common structural motif in proteins. For example, it occurs in human
growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
and several varieties of
cytochrome
Cytochromes are redox-active proteins containing a heme, with a central Fe atom at its core, as a cofactor. They are involved in electron transport chain and redox catalysis. They are classified according to the type of heme and its mode of bin ...
. The
Rop protein
Rop (also known as repressor of primer, or as RNA one modulator (ROM)) is a small dimeric protein responsible for keeping the copy number of ColE1 family and related bacterial plasmids low in '' E. coli'' by increasing the speed of pairing betwee ...
, which promotes plasmid replication in bacteria, is an interesting case in which a single polypeptide forms a coiled-coil and two monomers assemble to form a four-helix bundle.
Facial arrangements
The amino acids that make up a particular helix can be plotted on a
helical wheel
A helical wheel is a type of plot or visual representation used to illustrate the properties of alpha helices in proteins.
The sequence of amino acids that make up a helical region of the protein's secondary structure are plotted in a rotating ...
, a representation that illustrates the orientations of the constituent amino acids (see the article for
leucine zipper
A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amin ...
for such a diagram). Often in
globular protein
In biochemistry, globular proteins or spheroproteins are spherical ("globe-like") proteins and are one of the common protein types (the others being fibrous, disordered and membrane proteins). Globular proteins are somewhat water-soluble (formi ...
s, as well as in specialized structures such as coiled-coils and
leucine zipper
A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amin ...
s, an α-helix will exhibit two "faces" one containing predominantly
hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, th ...
amino acids oriented toward the interior of the protein, in the
hydrophobic core
The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and exclude water molecules. The word hydrophobic literally means "water-fearing", and it describes the segregation of water and nonpolar ...
, and one containing predominantly
polar
Polar may refer to:
Geography
Polar may refer to:
* Geographical pole, either of two fixed points on the surface of a rotating body or planet, at 90 degrees from the equator, based on the axis around which a body rotates
* Polar climate, the c ...
amino acids oriented toward the
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
-exposed surface of the protein.
Changes in binding orientation also occur for facially-organized oligopeptides. This pattern is especially common in
antimicrobial peptides
Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for a ...
, and many models have been devised to describe how this relates to their function. Common to many of them is that the hydrophobic face of the antimicrobial peptide forms pores in the plasma membrane after associating with the fatty chains at the membrane core.
Larger-scale assemblies
Myoglobin
Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is distantly related to hemoglobin. Compared to hemoglobin, myoglobi ...
and
hemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
, the first two proteins whose structures were solved by X-ray
crystallography
Crystallography is the experimental science of determining the arrangement of atoms in crystalline solids. Crystallography is a fundamental subject in the fields of materials science and solid-state physics (condensed matter physics). The wor ...
, have very similar folds made up of about 70% α-helix, with the rest being non-repetitive regions, or "loops" that connect the helices. In classifying proteins by their dominant fold, th
Structural Classification of Proteinsdatabase maintains a large category specifically for all-α proteins.
Hemoglobin then has an even larger-scale
quaternary structure
Protein quaternary structure is the fourth (and highest) classification level of protein structure. Protein quaternary structure refers to the structure of proteins which are themselves composed of two or more smaller protein chains (also refe ...
, in which the functional oxygen-binding molecule is made up of four subunits.
Functional roles
DNA binding
α-Helices have particular significance in
DNA binding motifs, including
helix-turn-helix
Helix-turn-helix is a DNA-binding protein (DBP). The helix-turn-helix (HTH) is a major structural motif capable of binding DNA. Each monomer incorporates two α helices, joined by a short strand of amino acids, that bind to the major groove of D ...
motifs,
leucine zipper
A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amin ...
motifs and
zinc finger
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...
motifs. This is because of the convenient structural fact that the diameter of an α-helix is about including an average set of sidechains, about the same as the width of the major groove in B-form
DNA, and also because
coiled-coil
A coiled coil is a structural motif in proteins in which 2–7
alpha helix, alpha-helices are coiled together like the strands of a rope. (Protein dimer, Dimers and Protein trimer, trimers are the most common types.) Many coiled coil-type protei ...
(or leucine zipper) dimers of helices can readily position a pair of interaction surfaces to contact the sort of symmetrical repeat common in double-helical DNA. An example of both aspects is the
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
Max (see image at left), which uses a helical coiled coil to dimerize, positioning another pair of helices for interaction in two successive turns of the DNA major groove.
Membrane spanning
α-Helices are also the most common protein structure element that crosses biological membranes (
transmembrane protein
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
), it is presumed because the helical structure can satisfy all backbone hydrogen-bonds internally, leaving no polar groups exposed to the membrane if the sidechains are hydrophobic. Proteins are sometimes anchored by a single membrane-spanning helix, sometimes by a pair, and sometimes by a helix bundle, most classically consisting of seven helices arranged up-and-down in a ring such as for
rhodopsin
Rhodopsin, also known as visual purple, is a protein encoded by the RHO gene and a G-protein-coupled receptor (GPCR). It is the opsin of the rod cells in the retina and a light-sensitive receptor protein that triggers visual phototransduction ...
s (see image at right) and other
G protein–coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
s (GPCRs). The structural stability between pairs of α-Helical transmembrane domains rely on conserved membrane interhelical packing motifs, for example, the Glycine-xxx-Glycine (or small-xxx-small) motif.
Mechanical properties
α-Helices under axial tensile deformation, a characteristic loading condition that appears in many alpha-helix-rich filaments and tissues, results in a characteristic three-phase behavior of stiff-soft-stiff tangent modulus. Phase I corresponds to the small-deformation regime during which the helix is stretched homogeneously, followed by phase II, in which alpha-helical turns break mediated by the rupture of groups of H-bonds. Phase III is typically associated with large-deformation covalent bond stretching.
Dynamical features
Alpha-helices in proteins may have
low-frequency accordion-like motion as observed by the
Raman spectroscopy
Raman spectroscopy () (named after Indian physicist C. V. Raman) is a spectroscopic technique typically used to determine vibrational modes of molecules, although rotational and other low-frequency modes of systems may also be observed. Raman sp ...
and analyzed via the quasi-continuum model.
Helices not stabilized by tertiary interactions show dynamic behavior, which can be mainly attributed to helix fraying from the ends.
Helix–coil transition
Homopolymers of amino acids (such as
polylysine
Polylysine refers to several types of lysine homopolymers, which may differ from each other in terms of stereochemistry (D/L; the L form is natural and usually assumed) and link position (α/ε). Of these types, only ε-poly-L-lysine is produced ...
) can adopt α-helical structure at low temperature that is "melted out" at high temperatures. This helix–coil transition was once thought to be analogous to protein
denaturation. The
statistical mechanics
In physics, statistical mechanics is a mathematical framework that applies statistical methods and probability theory to large assemblies of microscopic entities. It does not assume or postulate any natural laws, but explains the macroscopic be ...
of this transition can be modeled using an elegant
transfer matrix
In applied mathematics, the transfer matrix is a formulation in terms of a block-Toeplitz matrix of the two-scale equation, which characterizes refinable functions. Refinable functions play an important role in wavelet theory and finite element t ...
method, characterized by two parameters: the propensity to initiate a helix and the propensity to extend a helix.
In art
At least five artists have made explicit reference to the α-helix in their work: Julie Newdoll in painting and
Julian Voss-Andreae
Julian Voss-Andreae (born 15 August 1970) is a German sculptor living and working in the U.S.
Life
Voss-Andreae's full first name is Johann Julian, in honor of his ancestor, German pastor Johann Valentin Andreae.
According to an interview with th ...
,
Bathsheba Grossman
Bathsheba Grossman (born 1966) is an American artist who creates sculptures using computer-aided design and three-dimensional modeling, with metal printing technology to produce sculpture in bronze and stainless steel. Her bronze sculptures a ...
, Byron Rubin, and Mike Tyka in sculpture.
San Francisco area artist Julie Newdoll,
who holds a degree in Microbiology with a minor in art, has specialized in paintings inspired by microscopic images and molecules since 1990. Her painting "Rise of the Alpha Helix" (2003) features human figures arranged in an α helical arrangement. According to the artist, "the flowers reflect the various types of sidechains that each amino acid holds out to the world".
This same metaphor is also echoed from the scientist's side: "β sheets do not show a stiff repetitious regularity but flow in graceful, twisting curves, and even the α-helix is regular more in the manner of a flower stem, whose branching nodes show the influence of environment, developmental history, and the evolution of each part to match its own idiosyncratic function."
Julian Voss-Andreae
Julian Voss-Andreae (born 15 August 1970) is a German sculptor living and working in the U.S.
Life
Voss-Andreae's full first name is Johann Julian, in honor of his ancestor, German pastor Johann Valentin Andreae.
According to an interview with th ...
is a German-born sculptor with degrees in experimental physics and sculpture. Since 2001 Voss-Andreae creates "protein sculptures" based on protein structure with the α-helix being one of his preferred objects. Voss-Andreae has made α-helix sculptures from diverse materials including bamboo and whole trees. A monument Voss-Andreae created in 2004 to celebrate the memory of
Linus Pauling
Linus Carl Pauling (; February 28, 1901August 19, 1994) was an American chemist, biochemist, chemical engineer, peace activist, author, and educator. He published more than 1,200 papers and books, of which about 850 dealt with scientific top ...
, the discoverer of the α-helix, is fashioned from a large steel beam rearranged in the structure of the α-helix. The , bright-red sculpture stands in front of Pauling's childhood home in
Portland, Oregon
Portland (, ) is a port city in the Pacific Northwest and the largest city in the U.S. state of Oregon. Situated at the confluence of the Willamette and Columbia rivers, Portland is the county seat of Multnomah County, the most populous co ...
.
Ribbon diagrams
Ribbon diagrams, also known as Richardson diagrams, are 3D schematic representations of protein structure and are one of the most common methods of protein depiction used today. The ribbon shows the overall path and organization of the protein b ...
of α-helices are a prominent element in the laser-etched crystal sculptures of protein structures created by artist
Bathsheba Grossman
Bathsheba Grossman (born 1966) is an American artist who creates sculptures using computer-aided design and three-dimensional modeling, with metal printing technology to produce sculpture in bronze and stainless steel. Her bronze sculptures a ...
, such as those of
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
,
hemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
, and
DNA polymerase
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create ...
. Byron Rubin is a former protein crystallographer now professional sculptor in metal of proteins, nucleic acids, and drug molecules many of which featuring α-helices, such as
subtilisin
Subtilisin is a protease (a protein-digesting enzyme) initially obtained from ''Bacillus subtilis''.
Subtilisins belong to subtilases, a group of serine proteases that – like all serine proteases – initiate the nucleophilic attack on the p ...
,
human growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
, and
phospholipase A2
The enzyme phospholipase A2 (EC 3.1.1.4, PLA2, systematic name phosphatidylcholine 2-acylhydrolase) catalyse the cleavage of fatty acids in position 2 of phospholipids, hydrolyzing the bond between the second fatty acid “tail” and the glyce ...
.
Mike Tyka is a computational biochemist at the
University of Washington
The University of Washington (UW, simply Washington, or informally U-Dub) is a public research university in Seattle, Washington.
Founded in 1861, Washington is one of the oldest universities on the West Coast; it was established in Seattle a ...
working with
David Baker. Tyka has been making sculptures of protein molecules since 2010 from copper and steel, including
ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
and a
potassium channel
Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...
tetramer.
See also
*
310 helix
*
Beta sheet
The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...
*
Davydov soliton
*
Folding (chemistry)
In chemistry, folding is the process by which a molecule assumes its shape or conformation. The process can also be described as intramolecular self-assembly, a type of molecular self-assembly, where the molecule is directed to form a specifi ...
*
Knobs into holes packing
A coiled coil is a structural motif in proteins in which 2–7
alpha helix, alpha-helices are coiled together like the strands of a rope. (Protein dimer, Dimers and Protein trimer, trimers are the most common types.) Many coiled coil-type protei ...
*
Pi helix
A pi helix (or π-helix) is a type of secondary structure found in proteins. Discovered by crystallographer Barbara Low in 1952 and once thought to be rare, short π-helices are found in 15% of known protein structures and are believed to be an ...
*
References
Further reading
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External links
NetSurfP ver. 1.1 – Protein Surface Accessibility and Secondary Structure Predictionsα-helix rotational angle calculatorArtist Julie Newdoll's websiteArtist Julian Voss-Andreae's website
{{DEFAULTSORT:Alpha Helix
Protein structural motifs
Helices