Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs
Copyright policy )Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs
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 β-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.
- University of California, San Francisco United States
- UNIVERSITY OF CHICAGO
- University of California, Irvine United States
- University of California System United States
- University of California, Santa Barbara
Models, Molecular, 570, Guanine, Protein Conformation, Recombinant Fusion Proteins, Bacterial Toxins, Peptide Elongation Factor Tu, Crystallography, X-Ray, Substrate Specificity, Structure-Activity Relationship, Protein Domains, RNA, Transfer, Models, Structural Biology, Information and Computing Sciences, Escherichia coli, Crystallography, Escherichia coli Proteins, Bacterial, Molecular, Biological Sciences, Transfer, Environmental sciences, Biological sciences, RNA, Bacterial, Infectious Diseases, Chemical sciences, X-Ray, RNA, Nucleic Acid Conformation, Biochemistry and Cell Biology, Environmental Sciences, Developmental Biology
Models, Molecular, 570, Guanine, Protein Conformation, Recombinant Fusion Proteins, Bacterial Toxins, Peptide Elongation Factor Tu, Crystallography, X-Ray, Substrate Specificity, Structure-Activity Relationship, Protein Domains, RNA, Transfer, Models, Structural Biology, Information and Computing Sciences, Escherichia coli, Crystallography, Escherichia coli Proteins, Bacterial, Molecular, Biological Sciences, Transfer, Environmental sciences, Biological sciences, RNA, Bacterial, Infectious Diseases, Chemical sciences, X-Ray, RNA, Nucleic Acid Conformation, Biochemistry and Cell Biology, Environmental Sciences, Developmental Biology
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