formylMet

FormylMet, commonly referred to as N-formylmethionine (fMet), is the formylated derivative of the amino acid methionine. It serves as the initiating amino acid in protein synthesis in most bacteria and in the organelles derived from endosymbiotic bacteria, such as mitochondria and chloroplasts. The formyl group is attached to the amino nitrogen of methionine, producing a distinct initiating residue.

Biochemical basis and initiation process

In bacteria, translation typically begins with a Met-tRNA^Met that is converted into the initiator form by formylation. The enzyme formyltransferase (also called transformylase) transfers a formyl group from 10-formyl-tetrahydrofolate to the amino group of Met-tRNA^Met, yielding fMet-tRNA^fMet. The ribosome recognizes this charged tRNA as the initiator, allowing the first peptide bond to form with the nascent polypeptide. After initiation, the formyl group is commonly removed by peptide deformylase, and in many proteins the initiator methionine is subsequently removed by methionine aminopeptidase, depending on the second residue.

Distribution and significance

N-formylmethionine is a hallmark of prokaryotic protein synthesis and of plastid and mitochondrial translation in eukaryotes. Eukaryotic cytosolic proteins generally use unformylated methionine to initiate synthesis. FormylMet also contributes to cellular signaling; N-formylated peptides can act as chemoattractants for immune cells via formyl peptide receptors.

Medical and research relevance

Some antibiotics target peptide deformylase, interfering with bacterial protein maturation. In research settings, formylMet is used to study initiation mechanisms and N-terminal processing, and formylated peptides serve as tools in receptor and immunology studies.