Crystal Structure of the VapBC Toxin–Antitoxin Complex from Shigella flexneri Reveals a Hetero-Octameric DNA-Binding Assembly

Christian Dienemann; Andreas Bøggild; Kristoffer S. Winther; Kenn Gerdes; Ditlev Brodersen

doi:10.1016/j.jmb.2011.10.024

Crystal Structure of the VapBC Toxin–Antitoxin Complex from Shigella flexneri Reveals a Hetero-Octameric DNA-Binding Assembly

Christian Dienemann, Andreas Bøggild, Kristoffer S. Winther, Kenn Gerdes, Ditlev Brodersen

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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Abstract

Toxin–antitoxin (TA) loci are common in archaea and prokaryotes and allow cells to rapidly adapt to changing environmental conditions through release of active regulators of metabolism. Many toxins are endonucleases that target cellular mRNA and tRNAs, while the antitoxins tightly wrap around the toxins to inhibit them under normal circumstances. The antitoxins bind to operators in the promoter regions of the cognate TA operon and thereby regulate transcription. For enteric vapBC TA loci, the VapC toxins specifically cleave tRNAfMet and thus down-regulate protein synthesis. Here, we describe the crystal structure of the intact Shigella flexneri VapBC TA complex, determined to 2.7 Å resolution. Both in solution and in the crystal structure, four molecules of each protein combine to form a large and globular hetero-octameric assembly with SpoVT/AbrB-type DNA-binding domains at each end and a total molecular mass of about 100 kDa. The structure provides new insights into the inhibition of VapC toxins by VapB and provides the molecular basis for understanding the transcriptional regulation conferred by VapB.

Originalsprog	Engelsk
Tidsskrift	Journal of Molecular Biology
Vol/bind	414
Nummer	5
Sider (fra-til)	713-722
Antal sider	10
ISSN	0022-2836
DOI	https://doi.org/10.1016/j.jmb.2011.10.024
Status	Udgivet - 16 dec. 2011

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10.1016/j.jmb.2011.10.024

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title = "Crystal Structure of the VapBC Toxin–Antitoxin Complex from Shigella flexneri Reveals a Hetero-Octameric DNA-Binding Assembly",

abstract = "Toxin–antitoxin (TA) loci are common in archaea and prokaryotes andallow cells to rapidly adapt to changing environmental conditions throughrelease of active regulators of metabolism. Many toxins are endonucleasesthat target cellular mRNA and tRNAs, while the antitoxins tightly wraparound the toxins to inhibit them under normal circumstances. Theantitoxins also bind to operators in the promoter regions of the cognateTA operon and thereby regulate transcription. For enteric vapBC TA loci, theVapC toxins specifically cleave tRNAfMet and thus down-regulate proteinsynthesis. Here, we describe the crystal structure of the intact Shigellaflexneri VapBC TA complex, determined to 2.7 {\AA} resolution. Both in solutionand in the crystal structure, four molecules of each protein combine to forma large and globular hetero-octameric assembly with SpoVT/AbrB-typeDNA-binding domains at each end and a total molecular mass of about100 kDa. The structure gives new insights into the inhibition of VapC toxinsby VapB and provides the molecular basis for understanding transcriptionalregulation through VapB dimerization.",

keywords = "RNA interferase, tRNA, protein–DNA interaction",

author = "Christian Dienemann and Andreas B{\o}ggild and Winther, {Kristoffer S.} and Kenn Gerdes and Ditlev Brodersen",

year = "2011",

month = dec,

day = "16",

doi = "10.1016/j.jmb.2011.10.024",

language = "English",

volume = "414",

pages = "713--722",

journal = "Journal of Molecular Biology",

issn = "0022-2836",

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Crystal Structure of the VapBC Toxin–Antitoxin Complex from Shigella flexneri Reveals a Hetero-Octameric DNA-Binding Assembly. / Dienemann, Christian; Bøggild, Andreas; Winther, Kristoffer S. et al.
I: Journal of Molecular Biology, Bind 414, Nr. 5, 16.12.2011, s. 713-722.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Crystal Structure of the VapBC Toxin–Antitoxin Complex from Shigella flexneri Reveals a Hetero-Octameric DNA-Binding Assembly

AU - Dienemann, Christian

AU - Bøggild, Andreas

AU - Winther, Kristoffer S.

AU - Gerdes, Kenn

AU - Brodersen, Ditlev

PY - 2011/12/16

Y1 - 2011/12/16

N2 - Toxin–antitoxin (TA) loci are common in archaea and prokaryotes andallow cells to rapidly adapt to changing environmental conditions throughrelease of active regulators of metabolism. Many toxins are endonucleasesthat target cellular mRNA and tRNAs, while the antitoxins tightly wraparound the toxins to inhibit them under normal circumstances. Theantitoxins also bind to operators in the promoter regions of the cognateTA operon and thereby regulate transcription. For enteric vapBC TA loci, theVapC toxins specifically cleave tRNAfMet and thus down-regulate proteinsynthesis. Here, we describe the crystal structure of the intact Shigellaflexneri VapBC TA complex, determined to 2.7 Å resolution. Both in solutionand in the crystal structure, four molecules of each protein combine to forma large and globular hetero-octameric assembly with SpoVT/AbrB-typeDNA-binding domains at each end and a total molecular mass of about100 kDa. The structure gives new insights into the inhibition of VapC toxinsby VapB and provides the molecular basis for understanding transcriptionalregulation through VapB dimerization.

AB - Toxin–antitoxin (TA) loci are common in archaea and prokaryotes andallow cells to rapidly adapt to changing environmental conditions throughrelease of active regulators of metabolism. Many toxins are endonucleasesthat target cellular mRNA and tRNAs, while the antitoxins tightly wraparound the toxins to inhibit them under normal circumstances. Theantitoxins also bind to operators in the promoter regions of the cognateTA operon and thereby regulate transcription. For enteric vapBC TA loci, theVapC toxins specifically cleave tRNAfMet and thus down-regulate proteinsynthesis. Here, we describe the crystal structure of the intact Shigellaflexneri VapBC TA complex, determined to 2.7 Å resolution. Both in solutionand in the crystal structure, four molecules of each protein combine to forma large and globular hetero-octameric assembly with SpoVT/AbrB-typeDNA-binding domains at each end and a total molecular mass of about100 kDa. The structure gives new insights into the inhibition of VapC toxinsby VapB and provides the molecular basis for understanding transcriptionalregulation through VapB dimerization.

KW - RNA interferase

KW - tRNA

KW - protein–DNA interaction

U2 - 10.1016/j.jmb.2011.10.024

DO - 10.1016/j.jmb.2011.10.024

M3 - Journal article

C2 - 22037005

SN - 0022-2836

VL - 414

SP - 713

EP - 722

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 5

ER -

Crystal Structure of the VapBC Toxin–Antitoxin Complex from Shigella flexneri Reveals a Hetero-Octameric DNA-Binding Assembly

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