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Publication Abstract from PubMed

Contact-dependent growth inhibition (CDI) is a mechanism of inter-cellular competition in which Gram-negative bacteria exchange polymorphic toxins using type V secretion systems. Here, we present structures of the CDI toxin from Escherichia coli NC101 in ternary complex with its cognate immunity protein and elongation factor Tu (EF-Tu). The toxin binds exclusively to domain 2 of EF-Tu, partially overlapping the site that interacts with the 3'-end of aminoacyl-tRNA (aa-tRNA). The toxin exerts a unique ribonuclease activity that cleaves the single-stranded 3'-end from tRNAs that contain guanine discriminator nucleotides. EF-Tu is required to support this tRNase activity in vitro, suggesting the toxin specifically cleaves substrate in the context of GTP.EF-Tu.aa-tRNA complexes. However, superimposition of the toxin domain onto previously solved GTP.EF-Tu.aa-tRNA structures reveals potential steric clashes with both aa-tRNA and the switch I region of EF-Tu. Further, the toxin induces conformational changes in EF-Tu, displacing a beta-hairpin loop that forms a critical salt-bridge contact with the 3'-terminal adenylate of aa-tRNA. Together, these observations suggest that the toxin remodels GTP.EF-Tu.aa-tRNA complexes to free the 3'-end of aa-tRNA for entry into the nuclease active site.

Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs.,Michalska K, Gucinski GC, Garza-Sanchez F, Johnson PM, Stols LM, Eschenfeldt WH, Babnigg G, Low DA, Goulding CW, Joachimiak A, Hayes CS Nucleic Acids Res. 2017 Sep 29;45(17):10306-10320. doi: 10.1093/nar/gkx700. PMID:28973472^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.