4p7d
Antitoxin HicB3 crystal structure
Structural highlights
FunctionPublication Abstract from PubMedThe mechanisms involved in the virulence of Y. pestis, the plague pathogen, are not fully understood. In previous research, we found that a Yersinia pestis mutant lacking the HicB3 (YPO3369) putative orphan antitoxin was attenuated for virulence in a murine model of bubonic plague. Toxin-antitoxin systems (TASs) are widespread in prokaryotes. Most bacterial species possess many TASs of several types. In type II TASs, the toxin protein is bound and neutralized by its cognate antitoxin protein in the cytoplasm. Here, we identify the hicA3 gene encoding the toxin neutralized by HicB3, and show that HicA3-HicB3 constitutes a new functional type II TAS in Y. pestis. Using biochemical and mutagenesis-based approaches, we demonstrate that the HicA3 toxin is an RNase with a catalytic histidine residue. HicB3 has two functions: it sequesters and neutralizes HicA3 by blocking its active site and it represses transcription of the hicA3B3 operon. Gel-shift assays and reporter fusion experiments indicate that the HicB3 antitoxin binds to two operators in the hicA3B3 promoter region. We solved the X-ray structures of HicB3 and the HicA3HicB3 complex, thus we present the first crystal structure of a TA complex from the HicAB-family. HicB3 forms a tetramer that can bind two HicA3 toxin molecules. HicA3 is monomeric and folds as a double-stranded-RNA-binding domain. HicB3 N-terminal domain occludes the HicA3 active site, whereas its C-terminal domain folds as a ribbon-helix-helix DNA binding motif. Functional and structural analysis of HicA3-HicB3, a novel toxin-antitoxin system of Yersinia pestis.,Bibi-Triki S, Li de la Sierra-Gallay I, Lazar N, Leroy A, Van Tilbeurgh H, Sebbane F, Pradel E J Bacteriol. 2014 Aug 11. pii: JB.01932-14. PMID:25112480[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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