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, res ...
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
Hydrogen is the chemical element wi ...
group (-NH
2) located at the end of a polypeptide. Within a peptide, the amine group is bonded to the
carboxylic
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyli ...
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 of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
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
Hydrogen is the chemical element wi ...
group and a
carboxylic group. Amino acids link to one another by
peptide bonds which form through a
dehydration reaction
In chemistry, a dehydration reaction is a chemical reaction that involves the loss of water from the reacting molecule or ion. Dehydration reactions are common processes, the reverse of a hydration reaction.
Dehydration reactions in organic ch ...
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
Hydrogen is the chemical element wi ...
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
Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ...
) 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
chloroplasts, the modified version
''N''-formylmethionine, fMet). However, some proteins are modified
posttranslationally, for example, by cleavage from a
protein precursor
A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein (or peptide) that can be turned into an active form by post-translational modification, such as breaking off a piece of the molecule or adding on another molecule ...
, 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. 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 a ...
s" that direct delivery of the protein to the proper
organelle. 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 for ...
. 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 The ''N''-end rule is a rule that governs the rate of protein degradation through recognition of the N-terminal residue of proteins. The rule states that the ''N''-terminal amino acid of a protein determines its half-life (time after which half of ...
.
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 membr ...
(SRP) and results in the targeting of the protein to the
secretory pathway 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classica ...
. In
eukaryotic cells
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 ...
, these proteins are synthesized at the rough
endoplasmic reticulum. In
prokaryotic cells
A prokaryote () is a Unicellular organism, single-celled organism that lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek language, Greek wikt:πρό#Ancient Greek, πρό (, 'before') a ...
, 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 ( ...
. In
chloroplasts, 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 thyl ...
s.
Mitochondrial targeting peptide
The N-terminal mitochondrial
targeting peptide (mtTP) allows the protein to be imported into the
mitochondrion.
Chloroplast targeting peptide
The N-terminal chloroplast targeting peptide (cpTP) allows for the protein to be imported into the
chloroplast.
N-terminal modifications
Protein N-termini can be modified co - or post-translationally. Modifications include the removal of initiator methionine (iMet) by
aminopeptidase
Aminopeptidases are enzymes that catalyze the cleavage of amino acids from the amino terminus ( N-terminus) of proteins or peptides (exopeptidases). They are widely distributed throughout the animal and plant kingdoms and are found in many subcel ...
s, attachment of small chemical groups such as
acetyl, propionylgroup, propionyl and
Methyl group, methyl, and the addition of membrane anchors, such as
palmitoyl and
myristoyl groups
N-terminal acetylation
N-terminal acetylation is a form of protein modification that can occur in both
prokaryote
A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Conne ...
s and
eukaryotes. It has been suggested that N-terminal acetylation can prevent a protein from following a
secretory pathway 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classica ...
.
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 ...
s, their cleavage site specificity, substrates, inhibitors and protein termini originating from their activity
References
{{Reflist
Post-translational modification
Proteins
Protein structure