A helix bundle is a small

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, res ...

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 structural domains. The three-helix bundle in the villin headpiece domain is only 36

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 ...

s long and is a common subject of study in

molecular dynamics Molecular dynamics (MD) is a computer simulation method for analyzing the physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamic "evolution" of th ...

simulations because its

microsecond A microsecond is a unit of time in the International System of Units (SI) equal to one millionth (0.000001 or 10−6 or ) of a second. Its symbol is μs, sometimes simplified to us when Unicode is not available. A microsecond is equal to 1000 ...

-scale folding time is within the timescales accessible to simulation. The 40-residue HIV accessory protein has a very similar fold and has also been the subject of extensive study. There is no general

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 ' ...

associated with three-helix bundles, so they cannot necessarily be predicted from sequence alone. Three-helix bundles often occur in

actin-binding protein Actin-binding proteins (also known as ABPs) are proteins that bind to actin. This may mean ability to bind actin monomers, or polymers, or both. Many actin-binding proteins, including α-actinin, β-spectrin, dystrophin, utrophin and fimbrin, do t ...

s and in DNA-binding proteins.

Four-helix bundles

Four-helix bundles typically consist of four helices packed in a

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 f ...

arrangement with a

steric Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...

ally close-packed hydrophobic core in the center. Pairs of adjacent helices are often additionally stabilized by salt bridges between charged amino acids. The helix axes typically are oriented about 20 degrees from their neighboring helices, a much shallower incline than in the larger helical structure of the globin fold.Branden C, Tooze J. (1999). ''Introduction to Protein Structure'' 2nd ed. Garland Publishing: New York, NY. The specific topology of the helices is dependent on the protein – helices that are adjacent in sequence are often antiparallel, although it is also possible to arrange antiparallel links between two pairs of parallel helices. Because dimeric coiled-coils are themselves relatively stable, four-helix bundles can be

dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * Julius Dimer ( ...

s of coiled-coil pairs, as in the Rop protein. Four-helix bundle can have thermal stability more than 100 °C. Other examples of four-helix bundles include

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 ...

ferritin Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. It is the primary ...

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 ...

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...

, and Lac repressor C-terminal. The four-helix bundle fold has proven an attractive target for de novo

protein design Protein design is the rational design of new protein molecules to design novel activity, behavior, or purpose, and to advance basic understanding of protein function. Proteins can be designed from scratch (''de novo'' design) or by making calcul ...

, with numerous de novo four-helix bundle proteins having been successfully designed by rational and by combinatorial methods. Although sequence is not conserved among four-helix bundles, sequence ''patterns'' tend to mirror those of coiled-coil structures in which every fourth and seventh residue is hydrophobic.

References

External links

SCOP cytochrome c fold

{{Protein tertiary structure Protein folds

Three-helix bundles

Four-helix bundles

See also

References

External links