Functional plasticity of antibacterial EndoU toxins #MMPMID29923643
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): 509-27 PMID29923643show ga
Bacteria 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?CTSTECO31 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?CTSTECO31 and other clade III toxins are specific anticodon nucleases that cleave tRNAGlu between nucleotides C37 and m2A38. 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.
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Mol+Microbiol 2018 ; 109 (4): 509-27
