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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...

, referring to the free

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

group (-NH₂) 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 often written as or , sometimes as with R referring to an organyl group (e. ...

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 The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

, 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 semantics, 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 English la ...

direction to the text direction, because when a protein is translated from

messenger RNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...

, 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

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 cha ...

s which form through a

dehydration reaction In chemistry, a dehydration reaction is a chemical reaction that involves the loss of an H2O from the reacting molecule(s) or ion(s). This reaction results in the release of the H2O as water. When the reaction involves the coupling of two molecu ...

that joins the carboxyl group of one amino acid to the

group of the next in a head-to-tail manner to form a

chain. The chain has two ends – an amine group, the N-terminus, and an unbound carboxyl group, the

. When a protein is translated from

, it is created from N-terminus to C-terminus. The amino end of an amino acid (on a charged

tRNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

) during the elongation stage of translation, attaches to the carboxyl end of the growing chain. Since the

start codon The start codon is the first codon of a messenger RNA (mRNA) transcript translated by a ribosome. The start codon always codes for methionine in eukaryotes and archaea and a ''N''-formylmethionine (fMet) in bacteria, mitochondria and plastids. ...

of the

genetic code Genetic code is a set of rules used by living cell (biology), cells to Translation (biology), translate information encoded within genetic material (DNA or RNA sequences of nucleotide triplets or codons) into proteins. Translation is accomplished ...

codes for the amino acid

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other non-essential amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine play ...

, most protein sequences start with a

(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 us ...

and

chloroplast A chloroplast () is a type of membrane-bound organelle, organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. Chloroplasts have a high concentration of chlorophyll pigments which captur ...

s, 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 Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...

during

protein biosynthesis Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the produc ...

. 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 ...

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 numerical digit, digits or both, sometimes including spaces or punctuation, inclu ...

s" that direct delivery of the protein to the proper

organelle In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to th ...

. 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 proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do ...

. 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 proteolysis, protein degradation through recognition of the N-terminal residue of proteins. The rule states that the N-terminus, ''N''-terminal amino acid of a protein determines its half-life (t ...

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 membrane ...

(SRP) and results in the targeting of the protein to the

secretory pathway Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell (biology), cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. Th ...

. In eukaryotic cells, these proteins are synthesized at the rough

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

. In prokaryotic cells, the proteins are exported across the

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

. In

s, signal peptides target proteins to the

thylakoid Thylakoids are membrane-bound compartments inside chloroplasts and cyanobacterium, cyanobacteria. They are the site of the light-dependent reactions of photosynthesis. Thylakoids consist of a #Membrane, thylakoid membrane surrounding a #Lumen, ...

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 cell (biology), cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosine tri ...

Chloroplast targeting peptide

The N-terminal chloroplast targeting peptide (cpTP) allows for the protein to be imported into the

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 N-terminus (beginning), of proteins or peptides. They are found in many organisms; in the cell, they are found in many organelles, in the cytosol (internal cellular f ...

s, attachment of small chemical groups such as

acetyl In organic chemistry, an acetyl group is a functional group denoted by the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, an acetyl grou ...

, propionyl and

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

, 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 (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Gree ...

s and

eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

s. It has been suggested that N-terminal acetylation can prevent a protein from following a

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, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

anchor to form N-acetylated proteins. The most common form of such modification is the addition of a palmitoyl group.

References

{{Reflist Post-translational modification Proteins Protein structure