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

Abstract

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.

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE Office of Science - Office of Biological and Environmental Research
OSTI Identifier:
1376057
DOE Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nucleic Acids Research; Journal Volume: 45; Journal Issue: 9
Country of Publication:
United States
Language:
English

Citation Formats

Batot, Gaëlle, Michalska, Karolina, Ekberg, Greg, Irimpan, Ervin M., Joachimiak, Grazyna, Jedrzejczak, Robert, Babnigg, Gyorgy, Hayes, Christopher S., Joachimiak, Andrzej, and Goulding, Celia W. The CDI toxin of Yersinia kristensenii is a novel bacterial member of the RNase A superfamily. United States: N. p., 2017. Web. doi:10.1093/nar/gkx230.
Batot, Gaëlle, Michalska, Karolina, Ekberg, Greg, Irimpan, Ervin M., Joachimiak, Grazyna, Jedrzejczak, Robert, Babnigg, Gyorgy, Hayes, Christopher S., Joachimiak, Andrzej, & Goulding, Celia W. The CDI toxin of Yersinia kristensenii is a novel bacterial member of the RNase A superfamily. United States. doi:10.1093/nar/gkx230.
Batot, Gaëlle, Michalska, Karolina, Ekberg, Greg, Irimpan, Ervin M., Joachimiak, Grazyna, Jedrzejczak, Robert, Babnigg, Gyorgy, Hayes, Christopher S., Joachimiak, Andrzej, and Goulding, Celia W. Mon . "The CDI toxin of Yersinia kristensenii is a novel bacterial member of the RNase A superfamily". United States. doi:10.1093/nar/gkx230.
@article{osti_1376057,
title = {The CDI toxin of Yersinia kristensenii is a novel bacterial member of the RNase A superfamily},
author = {Batot, Gaëlle and Michalska, Karolina and Ekberg, Greg and Irimpan, Ervin M. and Joachimiak, Grazyna and Jedrzejczak, Robert and Babnigg, Gyorgy and Hayes, Christopher S. and Joachimiak, Andrzej and Goulding, Celia W.},
abstractNote = {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.},
doi = {10.1093/nar/gkx230},
journal = {Nucleic Acids Research},
number = 9,
volume = 45,
place = {United States},
year = {Mon Apr 10 00:00:00 EDT 2017},
month = {Mon Apr 10 00:00:00 EDT 2017}
}