N-terminal
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The N-terminus (also known as the amino-terminus, NH2-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 Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...
group (-NH2) 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 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 Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...
group and a
carboxylic group 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. Carboxylic ...
. Amino acids link to one another by peptide bonds 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 ...
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 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 ...
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 codes for the amino acid methionine, most protein sequences start with a methionine (or, in bacteria,
mitochondria 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 used ...
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 i ...
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. It often contains
signal peptide A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-te ...
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. The signal peptide is typically removed at the destination by a signal peptidase. 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 memb ...
(SRP) and results in the targeting of the protein to the secretory pathway. 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 The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – 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 (t ...
. 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 i ...
s, signal peptides target proteins to the thylakoids.


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 i ...
.


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 sub ...
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 : 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
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 & Con ...
s 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. Bacter ...
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, f ...
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 TopFIND is the Termini oriented protein Function Inferred Database (TopFIND) is an integrated knowledgebase focused on protein termini, their formation by proteases and functional implications. It contains information about the processing and t ...
, 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