4ntq
From Proteopedia
CdiA-CT/CdiI toxin and immunity complex from Enterobacter cloacae
Structural highlights
FunctionCDIA_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). Publication Abstract from PubMedContact-dependent growth inhibition (CDI) is one mechanism of inter-bacterial competition. CDI(+) cells export large CdiA effector proteins, which carry a variety of C-terminal toxin domains (CdiA-CT). CdiA-CT toxins are specifically neutralized by cognate CdiI immunity proteins to protect toxin-producing cells from autoinhibition. Here, we use structure determination to elucidate the activity of a CDI toxin from Enterobacter cloacae (ECL). The structure of CdiA-CT(ECL) resembles the C-terminal nuclease domain of colicin E3, which cleaves 16S ribosomal RNA to disrupt protein synthesis. In accord with this structural homology, we show that CdiA-CT(ECL) uses the same nuclease activity to inhibit bacterial growth. Surprisingly, although colicin E3 and CdiA(ECL) carry equivalent toxin domains, the corresponding immunity proteins are unrelated in sequence, structure, and toxin-binding site. Together, these findings reveal unexpected diversity among 16S rRNases and suggest that these nucleases are robust and versatile payloads for a variety of toxin-delivery platforms. CdiA from Enterobacter cloacae Delivers a Toxic Ribosomal RNase into Target Bacteria.,Beck CM, Morse RP, Cunningham DA, Iniguez A, Low DA, Goulding CW, Hayes CS Structure. 2014 May 6;22(5):707-18. doi: 10.1016/j.str.2014.02.012. Epub 2014 Mar, 20. PMID:24657090[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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