We identified a glucosyltransferase (YGT) and an ADP-ribosyltransferase (YART) in , highly related to glucosylating toxins from , the cause of antibiotics-associated enterocolitis. Both toxins consist of an amino-terminal enzyme domain, an autoprotease domain activated by inositol hexakisphosphate, and a carboxyl-terminal translocation domain. YGT -acetylglucosaminylates Rab5 and Rab31 at Thr and Thr, respectively, thereby inactivating the Rab proteins. YART ADP-ribosylates Rab5 and Rab31 at Gln and Gln, respectively. This activates Rab proteins by inhibiting GTP hydrolysis. We determined the crystal structure of the glycosyltransferase domain of YGT (YGT) in the presence and absence of UDP at 1.9- and 3.4-Å resolution, respectively. Thereby, we identified a previously unknown potassium ion-binding site, which explains potassium ion-dependent enhanced glycosyltransferase activity in clostridial and related toxins. Our findings exhibit a novel type of inverse regulation of Rab proteins by toxins and provide new insights into the structure-function relationship of glycosyltransferase toxins.
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| http://dx.doi.org/10.1126/sciadv.aaz2094 | DOI Listing |
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