Doc of Prophage P1 Is Inhibited by Its Antitoxin Partner Phd through Fold Complementation

被引：99

作者：

Garcia-Pino, Abel ^{[1
,2
]}

Christensen-Dalsgaard, Mikkel ^{[3
,4
]}

Wyns, Lode ^{[1
,2
]}

Yarmolinsky, Michael ^{[5
]}

Magnuson, Roy David ^{[6
]}

Gerdes, Kenn ^{[3
]}

Loris, Remy ^{[1
,2
]}

机构：

[1] Vrije Univ Brussel, Lab Ultrastruct, B-1050 Brussels, Belgium

[2] Vlaams Interuniv Inst Biotechnol VIB, Dept Mol & Cellular Interact, B-1050 Brussels, Belgium

[3] Univ Newcastle, Sch Med, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[4] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark

[5] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA

[6] Univ Alabama, Dept Biol Sci, Huntsville, AL 35899 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 45期

基金：

美国国家卫生研究院; 新加坡国家研究基金会;

关键词：

D O I：

10.1074/jbc.M805654200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Prokaryotic toxin-antitoxin modules are involved in major physiological events set in motion under stress conditions. The toxin Doc (death on curing) from the phd/doc module on phage P1 hosts the C-terminal domain of its antitoxin partner Phd (prevents host death) through fold complementation. This Phd domain is intrinsically disordered in solution and folds into an alpha-helix upon binding to Doc. The details of the interactions reveal the molecular basis for the inhibitory action of the antitoxin. The complex resembles the Fic (filamentation induced by cAMP) proteins and suggests a possible evolutionary origin for the phd/doc operon. Doc induces growth arrest of Escherichia coli cells in a reversible manner, by targeting the protein synthesis machinery. Moreover, Doc activates the endogenous E. coli RelE mRNA interferase but does not require this or any other known chromosomal toxin-antitoxin locus for its action in vivo.

引用

页码：30821 / 30827

页数：7

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