ホルミルメチオニン formylmethionine

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/25 16:21:55」(JST)

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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).^[2] 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 N-Formylmethionine, and use them to initiate phagocytosis.^[3]^[4]^[5]

A recent study published in Nature magazine ^[6] shows that 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. 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 (see Polly Matzinger ).

References

^ PMID: 20203610
^ 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.
^ Immunology at MCG 1/phagstep
^ "The Innate Immune System: Pattern-Recognition Receptors, Antigen-Nonspecific Antimicrobial Body Molecules, and Cytokines".
^ 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. PMC 2114803. PMID 2958480.
^ Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010 Mar 4;464(7285):104-7

External links

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

UpToDate Contents

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1. 自然免疫系の概要 an overview of the innate immune system
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3. 敗血症の病態生理 pathophysiology of sepsis
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English Journal

Kinetic modelling of mitochondrial translation.

Korla K1, Mitra CK.
Journal of biomolecular structure & dynamics.J Biomol Struct Dyn.2014 Oct;32(10):1634-50. doi: 10.1080/07391102.2013.833135. Epub 2013 Sep 13.
Mitochondrial genome contains 13 protein coding genes, all being part of the oxidative phosphorylation complexes. The process of translation of these protein coding mRNAs in mitochondrial matrix is a good miniature model of translation in cytoplasm. In this work, we have simulated three phases of mi
PMID 24028553

How many initiator tRNA genes does Escherichia coli need?

Samhita L1, Nanjundiah V2, Varshney U3.
Journal of bacteriology.J Bacteriol.2014 Jul;196(14):2607-15. doi: 10.1128/JB.01620-14. Epub 2014 May 9.
Multiple copies of a gene require enhanced investment on the part of the cell and, as such, call for an explanation. The observation that Escherichia coli has four copies of initiator tRNA (tRNAi) genes, encoding a special tRNA (tRNA(fMet)) required to start protein synthesis, is puzzling particular
PMID 24816600

In situ monitoring of structural changes during formation of 30S translation initiation complex by energy dissipation measurement using 27-MHz quartz-crystal microbalance.

Furusawa H1, Tsuyuki Y, Takahashi S, Okahata Y.
Analytical chemistry.Anal Chem.2014 Jun 3;86(11):5406-15. doi: 10.1021/ac500487b. Epub 2014 May 12.
Ribosome is a bionanomachine that facilitates an orderly translation process during protein synthesis in living cells. Real-time monitoring of conformational changes in ribosomal subunits in aqueous solution is important to understand the regulatory mechanism of protein synthesis, because conformati
PMID 24794712

Japanese Journal

Post-translational Chemical Construction of Backbone-thioester for DNA-programmed Synthesis of Backbone-cyclized Non-natural Peptides

KAWAKAMI Takashi,OHTA Atsushi,ASHIGAI Hiroshi,MURAKAMI Hiroshi,SUGA Hiroaki
Peptide science : proceedings of the ... Japanese Peptide Symposium 2008, 55-56, 2009-03-01
NAID 10027165922

新規クラス抗菌薬リネゾリド(ザイボックス^【○!R】)の抗菌作用および臨床効果

入野田一彦,野村俊治,橋本宗弘
日本薬理学雑誌 120(4), 245-252, 2002-10-01
… シド，クロラムフェニコール系薬剤は，細菌のタンパクがリボソームで合成される段階の30S及び50Sリボソームに結合してelongation cycle（伸長過程）を阻害するのに対し，リネゾリドはリボソームの50S，30S-mRNA，fMet-tRNAの三者が形成される過程を阻害し，かつ伸長過程を阻害しない．リネゾリドはこの特有な作用機序を有することにより，既存の抗菌薬群に対して耐性を有する菌にも交叉耐性を示すことなく，また，耐性 …
NAID 10010332279

各種刺激物質によって誘導されたハンドウイルカ好中球の呼吸バースト活性(免疫学)

白石力也,伊藤琢也,杉澤仁 [他],庄司洋子,遠藤智子,酒井健夫
The journal of veterinary medical science 64(8), 711-714, s・v, 2002-08-25
… 各種刺激物質によって誘導されたハンドウイルカ好中球の呼吸バースト活性を測定した.イルカ好中球の活性酸素産生は,ホルボールエステル,コンカナバリンA,加熱処理血漿,およびオプソニン化ザイモザン刺激により誘導されたが,fMet-Leu-Pheに対しては全く反応しなかった.リポポリサッカライドおよび黄色ブドウ球菌で刺激したイルカ好中球の活性酸素産生量は,ウシおよびヒト好中球に比べて少なかった. …
NAID 110003920903

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リンク元	「ホルミルメチオニン」「N-ホルミルメチオニン」「formylmethionine」
拡張検索	「N-fMet」
関連記事	「fM」

「ホルミルメチオニン」

N-Formylmethionine
	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 number	4289-98-9
PubChem	911
EC number	224-322-8
Jmol-3D images	Image 1
	SMILES CSCCC(NC=O)C(O)=O ;
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