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Crystal structure of VapBC2 from Rickettsia felis bound to a DNA fragment from their promoter
Structural highlights
FunctionVAPC2_RICFE Toxic component of a type II toxin-antitoxin (TA) system. Has ssRNase activity. Upon expression in E.coli or S.cerevisiae inhibits growth in liquid culture; in S.cerevisiae its expression leads to apoptosis-like characteristics. Rapidly induces apoptosis (within 2 hours) upon microinjection into mouse fibroblasts (L929 line); pretreatment of cells with dexamethasone protects them. Probably contributes to host cell death if bacterial cell lysis occurs during host infection. Its toxic effect is neutralized by coexpression with cognate antitoxin VapB2, its RNase activity is partially inhibited in vitro by VapB2 (PubMed:22046301).[HAMAP-Rule:MF_00265][1] Publication Abstract from PubMedBesides their commonly attributed role in the maintenance of low-copy number plasmids, toxin/antitoxin (TA) loci, also called 'addiction modules', have been found in chromosomes and associated to a number of biological functions such as: reduction of protein synthesis, gene regulation and retardation of cell growth under nutritional stress. The recent discovery of TA loci in obligatory intracellular species of the Rickettsia genus has prompted new research to establish whether they work as stress response elements or as addiction systems that might be toxic for the host cell. VapBC2 is a TA locus from R. felis, a pathogen responsible for flea-borne spotted fever in humans. The VapC2 toxin is a PIN-domain protein, whereas the antitoxin, VapB2, belongs to the family of swapped-hairpin beta-barrel DNA-binding proteins. We have used a combination of biophysical and structural methods to characterize this new toxin/antitoxin pair. Our results show how VapB2 can block the VapC2 toxin. They provide a first structural description of the interaction between a swapped-hairpin beta-barrel protein and DNA. Finally, these results suggest how the VapC2/VapB2 molar ratio can control the self-regulation of the TA locus transcription. Crystal structure of the DNA-bound VapBC2 antitoxin/toxin pair from Rickettsia felis.,Mate MJ, Vincentelli R, Foos N, Raoult D, Cambillau C, Ortiz-Lombardia M Nucleic Acids Res. 2012 Apr 1;40(7):3245-58. Epub 2011 Dec 2. PMID:22140099[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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