The N-terminus (also known as the amino-terminus, NH
2-terminus, N-terminal end or amine-terminus) is the start of a
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, respon ...
or
polypeptide, referring to the free
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...
group (-NH
2) located at the end of a polypeptide. Within a peptide, the amine group is bonded to the
carboxylic group of another amino acid, making it a chain. That leaves a free carboxylic group at one end of the peptide, called the
C-terminus, and a free amine group on the other end called the N-terminus. By convention, peptide sequences are written N-terminus to
C-terminus, left to right (in
LTR writing systems). This correlates the
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
direction to the text direction, because when a protein is translated from
messenger RNA, it is created from the N-terminus to the C-terminus, as amino acids are added to the carboxyl end of the protein.
Chemistry
Each amino acid has an
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...
group and a
carboxylic group. Amino acids link to one another by
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 c ...
s which form through a
dehydration reaction that joins the carboxyl group of one amino acid to the
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...
group of the next in a head-to-tail manner to form a
polypeptide chain. The chain has two ends – an amine group, the N-terminus, and an unbound carboxyl group, the
C-terminus.
When a protein is
translated from
messenger RNA, it is created from N-terminus to C-terminus. The amino end of an amino acid (on a charged
tRNA) during the elongation stage of translation, attaches to the carboxyl end of the growing chain. Since the
start codon of the
genetic code
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
codes for the amino acid
methionine, most protein sequences start with a
methionine (or, in bacteria,
mitochondria and
chloroplast
A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant and algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, and stores it ...
s, the modified version
''N''-formylmethionine, fMet). However, some proteins are modified
posttranslationally, for example, by cleavage from a
protein precursor, and therefore may have different amino acids at their N-terminus.
Function
N-terminal targeting signals
The N-terminus is the first part of the protein that exits the
ribosome during
protein biosynthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical ...
. It often contains
signal peptide sequences, "intracellular
postal code
A postal code (also known locally in various English-speaking countries throughout the world as a postcode, post code, PIN or ZIP Code) is a series of letters or digits or both, sometimes including spaces or punctuation, included in a postal ...
s" that direct delivery of the protein to the proper
organelle
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' t ...
. The signal peptide is typically removed at the destination by a signal
peptidase
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
. The N-terminal amino acid of a protein is an important determinant of its half-life (likelihood of being degraded). This is called the
N-end rule.
Signal peptide
The N-terminal signal peptide is recognized by the
signal recognition particle
The signal recognition particle (SRP) is an abundant, cytosolic, universally conserved ribonucleoprotein (protein-RNA complex) that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membra ...
(SRP) and results in the targeting of the protein to the
secretory pathway. In
eukaryotic cells, these proteins are synthesized at the rough
endoplasmic reticulum. In
prokaryotic cells, the proteins are exported across the
cell 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 (the ...
. In
chloroplast
A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant and algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, and stores it ...
s, signal peptides target proteins to the
thylakoid
Thylakoids are membrane-bound compartments inside chloroplasts and cyanobacteria. They are the site of the light-dependent reactions of photosynthesis. Thylakoids consist of a thylakoid membrane surrounding a thylakoid lumen. Chloroplast thyla ...
s.
Mitochondrial targeting peptide
The N-terminal mitochondrial
targeting peptide (mtTP) allows the protein to be imported into the
mitochondrion
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...
.
Chloroplast targeting peptide
The N-terminal chloroplast targeting peptide (cpTP) allows for the protein to be imported into the
chloroplast
A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant and algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, and stores it ...
.
N-terminal modifications
Protein N-termini can be modified co - or post-translationally. Modifications include the removal of initiator methionine (iMet) by
aminopeptidases, attachment of small chemical groups such as
acetyl, propionylgroup, propionyl and
Methyl group, methyl, and the addition of membrane anchors, such as
palmitoyl
Palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine (''S''-palmitoylation) and less frequently to serine and threonine (''O''-palmitoylation) residues of proteins, which are typically membrane proteins ...
and
myristoyl groups
N-terminal acetylation
N-terminal acetylation
:
In organic chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply ''acetates''. Deacetylation is the opposit ...
is a form of protein modification that can occur in both
prokaryotes and
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bact ...
s. It has been suggested that N-terminal acetylation can prevent a protein from following a
secretory pathway.
N-Myristoylation
The N-terminus can be modified by the addition of a myristoyl anchor. Proteins that are modified this way contain a consensus motif at their N-terminus as a modification signal.
N-Acylation
The N-terminus can also be modified by the addition of a
fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...
anchor to form N-acetylated proteins. The most common form of such modification is the addition of a palmitoyl group.
See also
*
C-terminus
*
TopFIND, a scientific database covering
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the form ...
s, their cleavage site specificity, substrates, inhibitors and protein termini originating from their activity
References
{{Reflist
Post-translational modification
Proteins
Protein structure