5hkq
Crystal structure of CDI complex from Escherichia coli STEC_O31
Structural highlights
FunctionCDIA_ECOST 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 target bacteria in a contact-dependent fashion (target cell counts decrease 1000- to 10000-fold with this CDI) (PubMed:28351921, PubMed:29923643). Uses outer membrane nucleoside transporter Tsx on target cells as a receptor (PubMed:28351921). Gains access to the cytoplasm of target cells by using integral inner membrane protein PTS system glucose-specific EIICB component (ptsG) (Probable). Targeting of the C-terminal domain (CT) domain (residues 2931-3253) in the absence of immunity protein inhibits cell growth and causes tRNA(UUC-Glu) cleavage; expression of cognate immunity protein CdiI-STECO31 neutralizes growth inhibition leaving tRNA(UUC-Glu) is intact, whereas non-cognate immunity proteins do not confer protection (PubMed:29923643). The CT domain cleaves tRNA; it is most active against tRNA(UUC-Glu), but also has modest activity against tRNA(GUC-Asp), tRNA(UUG-Gln), tRNA(CCC-Gly), tRNA(UCC-Gly), tRNA(GCC-Gly), tRNA(UUU-Lys), tRNA(GGU-Thr) and tRNA(CCA-Trp); tRNA cleavage is inhibited by cognate immunity protein CdiI. Cleavage of tRNA(UUC-Glu) occurs in the anticodon loop between cytosine(37) and 2-methyladenosine(38) (C37-m2A38) and probably also occurs in the anticodon loop of other tRNAs as well (PubMed:29923643).[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 (33 nm long) 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 (Tsx for this CDI) a signal is transmitted to activate secretion. The filament becomes about 5 nm longer, 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 (PTS system glucose-specific EIICB component, ptsG for this CDI).[4] Publication Abstract from PubMedBacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact-dependent growth inhibition toxin CdiA-CT(STECO31) from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15. The toxin contains a canonical His-His-Lys catalytic triad in the same arrangement as eukaryotic EndoU domains, but lacks the uridylate-specific ribonuclease activity that characterizes the superfamily. Comparative sequence analysis indicates that bacterial EndoU domains segregate into at least three major clades based on structural variations in the N-terminal subdomain. Representative EndoU nucleases from clades I and II degrade tRNA molecules with little specificity. In contrast, CdiA-CT(STECO31) and other clade III toxins are specific anticodon nucleases that cleave tRNA(Glu) between nucleotides C37 and m(2) A38. These findings suggest that the EndoU fold is a versatile scaffold for the evolution of novel substrate specificities. Such functional plasticity may account for the widespread use of EndoU effectors by diverse inter-bacterial toxin delivery systems. Functional plasticity of antibacterial EndoU toxins.,Michalska K, Quan Nhan D, Willett JLE, Stols LM, Eschenfeldt WH, Jones AM, Nguyen JY, Koskiniemi S, Low DA, Goulding CW, Joachimiak A, Hayes CS Mol Microbiol. 2018 Aug;109(4):509-527. doi: 10.1111/mmi.14007. Epub 2018 Aug 12. PMID:29923643[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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