The CDI toxin of Yersinia kristensenii is a novel bacterial member of the RNase A superfamily

Journal Article · Mon Apr 10 00:00:00 EDT 2017 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkx230· OSTI ID:1376057

Batot, Gaëlle; Michalska, Karolina; Ekberg, Greg; Irimpan, Ervin M.; Joachimiak, Grazyna; Jedrzejczak, Robert; Babnigg, Gyorgy; Hayes, Christopher S.; Joachimiak, Andrzej; Goulding, Celia W.

Contact-dependent growth inhibition (CDI) is an important mechanism of inter-bacterial competition found in many Gram-negative pathogens. CDI+ cells express cell-surface CdiA proteins that bind neighboring bacteria and deliver C-terminal toxin domains (CdiA-CT) to inhibit target-cell growth. CDI+ bacteria also produce CdiI immunity proteins, which specifically neutralize cognate CdiA-CT toxins to prevent self-inhibition. Here, we present the crystal structure of the CdiA-CT/CdiI(Ykris) complex from Yersinia kris-tensenii ATCC 33638. CdiA-CTYkris adopts the same fold as angiogenin and other RNase A paralogs, but the toxin does not share sequence similarity with these nucleases and lacks the characteristic disulfide bonds of the superfamily. Consistent with the structural homology, CdiA-CTYkris has potent RNase activity in vitro and in vivo. Structure-guided mutagenesis reveals that His175, Arg186, Thr276 and Tyr278 contribute to CdiA-CTYkris activity, suggesting that these residues participate in substrate binding and/or catalysis. CdiI(Ykris) binds directly over the putative active site and likely neutralizes toxicity by blocking access to RNA substrates. Significantly, CdiA-CTYkris is the first non-vertebrate protein found to possess the RNase A superfamily fold, and homologs of this toxin are associated with secretion systems in many Gram-negative and Gram-positive bacteria. These observations suggest that RNase Alike toxins are commonly deployed in inter-bacterial competition.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States)
• Sponsoring Organization: National Institutes of Health (NIH); USDOE Office of Science - Office of Biological and Environmental Research
• DOE Contract Number: AC02-06CH11357
• OSTI ID: 1376057
• Journal Information: Nucleic Acids Research, Vol. 45, Issue 9; ISSN 0305-1048
• Publisher: Oxford University Press
• Country of Publication: United States
• Language: English