N-Formylmethionine

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N-Formylmethionine
(S)-N-Formylmethionine V.1.svg
Identifiers
Abbreviations fMet
CAS number 4289-98-9 YesY
PubChem 911
EC number 224-322-8
Jmol-3D images Image 1
Properties
Molecular formula C6H11NO3S
Molar mass 177.22 g mol−1
Supplementary data page
Structure and
properties
n, εr, etc.
Thermodynamic
data
Phase behaviour
Solid, liquid, gas
Spectral data UV, IR, NMR, MS
Except where noted otherwise, data are 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[edit]

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 (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).[1] Before aminopeptidase can remove the N-terminal methionine, it must be deformylated by peptide deformylase.

Relevance to immunology[edit]

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[edit]

  1. ^ Sherman F, Stewart JW, Tsunasawa S (July 1985). "Methionine or not methionine at the beginning of a protein". BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology 3 (1): 27–31. doi:10.1002/bies.950030108. PMID 3024631. 
  2. ^ Immunology at MCG 1/phagstep
  3. ^ "The Innate Immune System: Pattern-Recognition Receptors, Antigen-Nonspecific Antimicrobial Body Molecules, and Cytokines". 
  4. ^ Detmers PA, Wright SD, Olsen E, Kimball B, Cohn ZA (September 1987). "Aggregation of complement receptors on human neutrophils in the absence of ligand". The Journal of Cell Biology 105 (3): 1137–45. doi:10.1083/jcb.105.3.1137. PMC 2114803. PMID 2958480. 
  5. ^ "Circulating mitochondrial DAMPs cause inflammatory responses to injury". Nature 464 (7285): 104–107. Mar 4, 2010. doi:10.1038/nature08780. 

External links[edit]