PDBsum entry 5e3e

Toxin

PDB id: 5e3e

Contents

Protein chains

99 a.a.

114 a.a.

94 a.a.

Metals

_NA ×2

Waters ×436

References listed in PDB file

Key reference

• Title: The cdi toxin of yersinia kristensenii is a novel bacterial member of the rnase a superfamily.
• Authors: G.Batot, K.Michalska, G.Ekberg, E.M.Irimpan, G.Joachimiak, R.Jedrzejczak, G.Babnigg, C.S.Hayes, A.Joachimiak, C.W.Goulding.
• Ref.: Nucleic Acids Res, 2017, 45, 5013-5025.
• PubMed id: 28398546

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/CdiIYkris complex from Yersinia kristensenii 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. CdiIYkris 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 A-like toxins are commonly deployed in inter-bacterial competition.