5i4q

Structural highlights

Function

CDIA_ECONC 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 about 10,0000-fold for this system). CdiA toxicity is neutralized by its cognate immunity protein CdiI-NC101, but not by CdiI from other bacteria (PubMed:26305955, PubMed:28973472). The C-terminal domain (CT) cleaves tRNA endonucleolytically at the 5' side of guanine discriminator nucleotide sites (removes the last 4 nucleotides of the tRNA acceptor arm when the first nucleotide to be removed is G) (PubMed:28973472). Requires EF-Ts (tsf) for toxic function of the CT domain in vivo (PubMed:28223500). In vitro the CT tRNase activity requires both EF-Tu (tufA) and EF-Ts. EF-Ts probably increases steady-state GTP-EF-Tu-aa-tRNA substrate levels. The CT domain is thought to remodel this same complex to displace the 3'-end of the aa-tRNA and allow it to enter into the toxin active site (PubMed:28973472). The CT domain gains access to the cytoplasm of target cells by using integral inner membrane protein PTS system glucose-specific EIICB component (ptsG) (PubMed:26305955).^{[1] [2] [3]} The CdiA protein is thought to be exported from the cell through the central lumen of CdiB, the other half of its two-partner system (TPS). The TPS domain probably remains associated with CdiB while the FHA-1 domain forms an extended filament with the receptor-binding domain (RBD) at its extremity; in the secretion arrested state the C-terminus of the RBD and YP domains form a hairpin-like structure as the FHA-2, PT and CT domains are periplasmic. The YP domain is probably responsible for this arrest at the point where it re-enters the host cell periplasm. Upon binding to a target cell outer membrane receptor a signal is transmitted to activate secretion. The filament elongates slightly, the rest of CdiA is secreted and the FHA-2 domain becomes stably associated with the target cell's outer membrane where it facilitates entry of the toxic CT domain into the target cell periplasm. From there the toxic CT domain is cleaved and gains access to the target cell cytoplasm via an inner membrane protein (PtsG for this CDI).^[4]

See Also

• Elongation factor 3D structures

References

1. ↑ Willett JL, Gucinski GC, Fatherree JP, Low DA, Hayes CS. Contact-dependent growth inhibition toxins exploit multiple independent cell-entry pathways. Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):11341-6. doi: , 10.1073/pnas.1512124112. Epub 2015 Aug 24. PMID:26305955 doi:http://dx.doi.org/10.1073/pnas.1512124112
2. ↑ Jones AM, Garza-Sánchez F, So J, Hayes CS, Low DA. Activation of contact-dependent antibacterial tRNase toxins by translation elongation factors. Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):E1951-E1957. PMID:28223500 doi:10.1073/pnas.1619273114
3. ↑ Michalska K, Gucinski GC, Garza-Sanchez F, Johnson PM, Stols LM, Eschenfeldt WH, Babnigg G, Low DA, Goulding CW, Joachimiak A, Hayes CS. Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs. Nucleic Acids Res. 2017 Sep 29;45(17):10306-10320. doi: 10.1093/nar/gkx700. PMID:28973472 doi:http://dx.doi.org/10.1093/nar/gkx700
4. ↑ Willett JL, Gucinski GC, Fatherree JP, Low DA, Hayes CS. Contact-dependent growth inhibition toxins exploit multiple independent cell-entry pathways. Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):11341-6. doi: , 10.1073/pnas.1512124112. Epub 2015 Aug 24. PMID:26305955 doi:http://dx.doi.org/10.1073/pnas.1512124112
5. ↑ Michalska K, Gucinski GC, Garza-Sanchez F, Johnson PM, Stols LM, Eschenfeldt WH, Babnigg G, Low DA, Goulding CW, Joachimiak A, Hayes CS. Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs. Nucleic Acids Res. 2017 Sep 29;45(17):10306-10320. doi: 10.1093/nar/gkx700. PMID:28973472 doi:http://dx.doi.org/10.1093/nar/gkx700