4ntq

Structural highlights

Function

CDIA_ENTCC 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; upon forced induction decreases E.cloacae target cell counts about 20-fold, about 100-fold in E.coli. Intracellular expression of CdiA-CT (residues 3087-3321) inhibits E.coli cell growth when induced, but coexpression with its cognate immunity protein CdiI allows cell growth. Cleaves 16S rRNA in vivo and in vitro between adenine 1493 and guanosine 1494 of E.coli 16S rRNA. Inhibition of 16S rRNA cleavage is specific to the cognate immunity protein, non-cognate CdiI from E.chrysanthemi strain EC16 does not inhibit this protein (PubMed:24657090). Purified CdiA-CT inhibits E.coli cell growth when added to cultures but not when added as a complex with cognate CdiI, suggesting cognate CdiI prevents import into the target cell. CdiA-CT (without CdiI) is probably imported in an F-pilus-mediated fashion, although it is not clear if this is physiologically significant (PubMed:24889811). Gains access to the cytoplasm of target cells by using integral inner membrane protein FtsH (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 (FtsH for this CDI).

References

1. ↑ Beck CM, Morse RP, Cunningham DA, Iniguez A, Low DA, Goulding CW, Hayes CS. CdiA from Enterobacter cloacae Delivers a Toxic Ribosomal RNase into Target Bacteria. Structure. 2014 May 6;22(5):707-18. doi: 10.1016/j.str.2014.02.012. Epub 2014 Mar, 20. PMID:24657090 doi:http://dx.doi.org/10.1016/j.str.2014.02.012
2. ↑ 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
3. ↑ 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
4. ↑ Beck CM, Morse RP, Cunningham DA, Iniguez A, Low DA, Goulding CW, Hayes CS. CdiA from Enterobacter cloacae Delivers a Toxic Ribosomal RNase into Target Bacteria. Structure. 2014 May 6;22(5):707-18. doi: 10.1016/j.str.2014.02.012. Epub 2014 Mar, 20. PMID:24657090 doi:http://dx.doi.org/10.1016/j.str.2014.02.012