5j43

Structural highlights

Function

[CDIA_ECOL5] Toxic component of a toxin-immunity protein module, which functions as a cellular contact-dependent growth inhibition (CDI) system. CDI modules allow bacteria to communicate with and inhibit the growth of closely related neighboring bacteria in a contact-dependent fashion (target cell counts decrease 100- to 1000-fold). CdiA toxicity is neutralized by its cognate immunity protein CdiI, but not by CdiI from other bacteria (PubMed:23469034, PubMed:24889811). BamA on the target cells acts as a receptor for intact CdiA (PubMed:23469034). However isolated CdiA-CT is imported in an F-pilus-mediated fashion; CdiA-CT inhibits F-mediated conjugation, probably via its N-terminus (residues 3016-3097), although it is not clear if this is physiologically significant (PubMed:24889811). The C-terminal domain (CT) cleaves within tRNA anticodon loops (PubMed:22333533, PubMed:24889811); this activity is inhibited by cognate CdiI (PubMed:21085179, PubMed:22333533, PubMed:24889811). tRNase activity of CdiA-CT is stimulated by CysK, although the extreme C-terminus (residues 3098-3242) has tRNase activity in the absence of CysK. In vivo CDI toxicity requires CysK (PubMed:22333533, PubMed:24889811). Purified CdiA-CT (residues 3016-3242) inhibits E.coli cell growth when added to cultures alone or in complex with cognate CdiI, growth is inhibited when cognate CdiI is present within the cell but not when a CdiA-CT/CdiI complex is added extracellularly, suggesting CdiA-CT alone but not the CdiA-CT/CdiI complex is imported into the target cell (PubMed:24889811).^{[1] [2] [3] [4] [5]}

References

1. ↑ Aoki SK, Diner EJ, de Roodenbeke CT, Burgess BR, Poole SJ, Braaten BA, Jones AM, Webb JS, Hayes CS, Cotter PA, Low DA. A widespread family of polymorphic contact-dependent toxin delivery systems in bacteria. Nature. 2010 Nov 18;468(7322):439-42. doi: 10.1038/nature09490. PMID:21085179 doi:http://dx.doi.org/10.1038/nature09490
2. ↑ Diner EJ, Beck CM, Webb JS, Low DA, Hayes CS. Identification of a target cell permissive factor required for contact-dependent growth inhibition (CDI). Genes Dev. 2012 Mar 1;26(5):515-25. doi: 10.1101/gad.182345.111. Epub 2012 Feb, 14. PMID:22333533 doi:http://dx.doi.org/10.1101/gad.182345.111
3. ↑ Webb JS, Nikolakakis KC, Willett JL, Aoki SK, Hayes CS, Low DA. Delivery of CdiA nuclease toxins into target cells during contact-dependent growth inhibition. PLoS One. 2013;8(2):e57609. doi: 10.1371/journal.pone.0057609. Epub 2013 Feb 28. PMID:23469034 doi:http://dx.doi.org/10.1371/journal.pone.0057609
4. ↑ Beck CM, Diner EJ, Kim JJ, Low DA, Hayes CS. The F pilus mediates a novel pathway of CDI toxin import. Mol Microbiol. 2014 Jul;93(2):276-90. doi: 10.1111/mmi.12658. Epub 2014 Jun 15. PMID:24889811 doi:http://dx.doi.org/10.1111/mmi.12658
5. ↑ Ruhe ZC, Nguyen JY, Beck CM, Low DA, Hayes CS. The proton-motive force is required for translocation of CDI toxins across the inner membrane of target bacteria. Mol Microbiol. 2014 Oct;94(2):466-81. doi: 10.1111/mmi.12779. Epub 2014 Sep 17. PMID:25174572 doi:http://dx.doi.org/10.1111/mmi.12779