N-formylmethionine

N-Formylmethionine(fMet) is an amino acid found in all living cells. It is a derivative of the amino acid methionine. It is a modified form of methionine in which a formyl group has been added to methionine's amino group.

It plays a crucial part in the protein synthesis of bacteria, mitochondria and chloroplasts. It is not used in the protein synthesis taking place in the cytosol of eukaryotes, where eukaryotic nuclear genes are translated.

Function in protein synthesis
fMet is a starting residue in the synthesis of proteins in prokaryotes 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 5'-CAU-3' anticodon that is capable of binding with the AUG start codon located on the mRNA.

N-Formylmethionine is coded by the same codon as methionine, AUG. However, AUG is also the translation initiation codon. When the codon is used for initiation, N-formylmethionine 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 transformylase. 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. 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.

Relevance to immunology
Because N-Formylmethionine 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 N-Formylmethionine, and use them to initiate phagocytosis.