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

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  • Christian Dienemann
  • Andreas Boggild
  • Kristoffer S. Winther
  • Kenn Gerdes
  • Ditlev E. Brodersen
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 also 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 tRNA(fMet) and thus down-regulate protein synthesis. Here, we describe the crystal structure of the intact Shigella flexneri VapBC TA complex, determined to 2.7 angstrom 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 gives new insights into the inhibition of VapC toxins by VapB and provides the molecular basis for understanding transcriptional regulation through VapB dimerization. (C) 2011 Elsevier Ltd. All rights reserved.
OriginalsprogEngelsk
TidsskriftJournal of Molecular Biology
Vol/bind414
Udgave nummer5
Sider (fra-til)713-722
Antal sider10
ISSN0022-2836
DOI
StatusUdgivet - 2011
Eksternt udgivetJa

ID: 95336708