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

Abel Garcia-Pino; Mikkel Christensen-Dalsgaard; Lode Wyns; Michael Yarmolinsky; Roy David Magnuson; Kenn Gerdes; Remy Loris

doi:10.1074/jbc.M805654200

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

Abel Garcia-Pino, Mikkel Christensen-Dalsgaard, Lode Wyns, Michael Yarmolinsky, Roy David Magnuson, Kenn Gerdes, Remy Loris

87 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Journal of Biological Chemistry
Vol/bind	283
Udgave nummer	45
Sider (fra-til)	30821-30827
Antal sider	7
ISSN	0021-9258
DOI	https://doi.org/10.1074/jbc.M805654200
Status	Udgivet - 2008
Udgivet eksternt	Ja

Adgang til dokumentet

10.1074/jbc.M805654200

Citationsformater

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title = "Doc of Prophage P1 Is Inhibited by Its Antitoxin Partner Phd through Fold Complementation",

abstract = "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.",

author = "Abel Garcia-Pino and Mikkel Christensen-Dalsgaard and Lode Wyns and Michael Yarmolinsky and Magnuson, {Roy David} and Kenn Gerdes and Remy Loris",

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T1 - Doc of Prophage P1 Is Inhibited by Its Antitoxin Partner Phd through Fold Complementation

AU - Garcia-Pino, Abel

AU - Christensen-Dalsgaard, Mikkel

AU - Wyns, Lode

AU - Yarmolinsky, Michael

AU - Magnuson, Roy David

AU - Gerdes, Kenn

AU - Loris, Remy

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.M805654200

DO - 10.1074/jbc.M805654200

M3 - Journal article

C2 - 18757857

SN - 0021-9258

VL - 283

SP - 30821

EP - 30827

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 45

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