N-Formylmethionine
Encyclopedia
N-Formylmethionine is a proteinogenic
amino acid
found in Bacteria
and related Prokaryotic organelles. It is a derivative of the amino acid
methionine
in which a formyl group has been added to the amino group. It is specifically used for initiation of protein synthesis, and may be removed after.
fMet plays a crucial part in the protein synthesis of bacteria, mitochondria
and chloroplast
s. It is not used in cytosol
ic protein synthesis of eukaryote
s, where eukaryotic nuclear gene
s are translated. It is also not used by Archaea
. In the human body, fMet is recognized by the immune system as foreign material and stimulates the body to fight against potential infection.
(30S) - mRNA complex by a specialized tRNA (tRNAfMet) which has a 3'-UAC-5' anticodon that is capable of binding with the 5'-AUG-3' start codon located on the mRNA.
fMet is coded by the same codon as methionine, AUG. However, AUG is also the translation initiation codon. When the codon is used for initiation, fMet is used instead of methionine, thereby forming the first amino acid of the nascent peptide
chain. When the same codon appears later in the mRNA, normal methionine is used. Many organisms use variations of this basic mechanism.
The addition of the formyl group to methionine is catalyzed by the enzyme
methionyl-tRNA formyltransferase
. This modification is done after methionine has been loaded onto tRNAfMet by aminoacyl-tRNA synthetase.
Note that methionine can be loaded either onto tRNAfMet or tRNAMet. However, transformylase will catalyze the addition of the formyl group to methionine only if methionine has been loaded onto tRNAfMet and NOT onto tRNAMet.
This methionine is removed from majority of proteins (both host and recombinant) by methionine aminopeptidase (MAP).
can use it to help distinguish self from non-self. Polymorphonuclear cells can bind proteins starting with N-Formylmethionine, and use them to initiate phagocytosis.
Proteinogenic amino acid
Proteinogenic amino acids are those amino acids that can be found in proteins and require cellular machinery coded for in the genetic code of any organism for their isolated production. There are 22 standard amino acids, but only 21 are found in eukaryotes. Of the 22, 20 are directly encoded by...
amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
found in Bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
and related Prokaryotic organelles. It is a derivative of the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
in which a formyl group has been added to the amino group. It is specifically used for initiation of protein synthesis, and may be removed after.
fMet plays a crucial part in the protein synthesis of bacteria, mitochondria
Mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...
and chloroplast
Chloroplast
Chloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.Chloroplasts are green...
s. It is not used in cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
ic protein synthesis of eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s, where eukaryotic nuclear gene
Nuclear gene
A Nuclear gene is a gene located in the cell nucleus of a eukaryote. The term is used to distinguish nuclear genes from the genes in the mitochondrion, and in case of plants, also the chloroplast, which host their own genetic system and can produce proteins from scratch...
s are translated. It is also not used by Archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
. In the human body, fMet is recognized by the immune system as foreign material and stimulates the body to fight against potential infection.
Function in protein synthesis
fMet is a starting residue in the synthesis of proteins in bacteria, and, consequently, is located at the N-terminus of the growing polypeptide. fMet is delivered to the ribosomeRibosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
(30S) - mRNA complex by a specialized tRNA (tRNAfMet) which has a 3'-UAC-5' anticodon that is capable of binding with the 5'-AUG-3' start codon located on the mRNA.
fMet is coded by the same codon as methionine, AUG. However, AUG is also the translation initiation codon. When the codon is used for initiation, fMet is used instead of methionine, thereby forming the first amino acid of the nascent peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
chain. When the same codon appears later in the mRNA, normal methionine is used. Many organisms use variations of this basic mechanism.
The addition of the formyl group to methionine is catalyzed by the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
methionyl-tRNA formyltransferase
Methionyl-tRNA formyltransferase
In enzymology, a methionyl-tRNA formyltransferase is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are 10-formyltetrahydrofolate, L-methionyl-tRNAfMet, and H2O, whereas its two products are tetrahydrofolate and N-formylmethionyl-tRNAfMet.This enzyme belongs to the...
. This modification is done after methionine has been loaded onto tRNAfMet by aminoacyl-tRNA synthetase.
Note that methionine can be loaded either onto tRNAfMet or tRNAMet. However, transformylase will catalyze the addition of the formyl group to methionine only if methionine has been loaded onto tRNAfMet and NOT onto tRNAMet.
This methionine is removed from majority of proteins (both host and recombinant) by methionine aminopeptidase (MAP).
Relevance to immunology
Because fMet is present in proteins made by prokaryotes but not in those made by eukaryotes, the immune systemImmune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
can use it to help distinguish self from non-self. Polymorphonuclear cells can bind proteins starting with N-Formylmethionine, and use them to initiate phagocytosis.