N-Formylmethionine

N-Formylmethionine

Names
IUPAC name (S)-2-Formylamino-4-methylsulfanylbutanoic acid
Other names 2-Formylamino-4-methylsulfanyl-butyric acid; Formylmethionine; N-Formyl(methyl)homocysteine
Identifiers
Abbreviations	fMet
CAS Registry Number	4289-98-9 Y
EC number	224-322-8
Jmol-3D images	Image
PubChem	911
SMILES CSCCC(NC=O)C(O)=O
Properties
Molecular formula	C6H11NO3S
Molar mass	177.22 g·mol−1
Supplementary data page
Structure and properties	Refractive index (n), Dielectric constant (εr), etc.
Thermodynamic data	Phase behaviour solid–liquid–gas
Spectral data	UV, IR, NMR, MS
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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Infobox references

N-Formylmethionine (fMet) 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 from bacterial and organellar genes, and may be removed post-translationally.

fMet plays a crucial part in the protein synthesis of bacteria, mitochondria and chloroplasts. It is not used in cytosolic protein synthesis of eukaryotes, where eukaryotic nuclear genes are translated. It is also not used by Archaea. In the human body, fMet is recognized by the immune system as foreign material, or as an alarm signal released by damaged cells, 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 ribosome (30S) - mRNA complex by a specialized tRNA (tRNA^fMet) 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 tRNA^fMet by aminoacyl-tRNA synthetase.

Note that methionine can be loaded either onto tRNA^fMet or tRNA^Met. However, transformylase will catalyze the addition of the formyl group to methionine only if methionine has been loaded onto tRNA^fMet and not onto tRNA^Met.

This methionine is removed from majority of proteins (both host and recombinant) by methionine aminopeptidase (MAP).^[1] Before aminopeptidase can remove the N-terminal methionine, it must be deformylated by peptide deformylase.

Relevance to immunology

Because fMet is present in proteins made by prokaryotes but not in those made by eukaryotes, the immune system can use it to help distinguish self from non-self. Polymorphonuclear cells can bind proteins starting with fMet, and use them to initiate phagocytosis.^[2][3][4]

fMet is present in proteins made by mitochondria, so it is no longer thought to be a molecule that the immune system can use to distinguish self from non-self.^[5] Instead, it appears to be a molecule that is released by the mitochondria of damaged tissues (and by damaged bacteria), and can thus qualify as an "alarm" signal, as discussed in the Danger model of immunity.

References

External links

• N-Formylmethionine at the US National Library of Medicine Medical Subject Headings (MeSH)