6rth

Publication Abstract from PubMed

We identified a glucosyltransferase (YGT) and an ADP-ribosyltransferase (YART) in Yersinia mollaretii, highly related to glucosylating toxins from Clostridium difficile, the cause of antibiotics-associated enterocolitis. Both Yersinia toxins consist of an amino-terminal enzyme domain, an autoprotease domain activated by inositol hexakisphosphate, and a carboxyl-terminal translocation domain. YGT N-acetylglucosaminylates Rab5 and Rab31 at Thr(52) and Thr(36), respectively, thereby inactivating the Rab proteins. YART ADP-ribosylates Rab5 and Rab31 at Gln(79) and Gln(64), respectively. This activates Rab proteins by inhibiting GTP hydrolysis. We determined the crystal structure of the glycosyltransferase domain of YGT (YGT(G)) in the presence and absence of UDP at 1.9- and 3.4-A 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.

Inverse control of Rab proteins by Yersinia ADP-ribosyltransferase and glycosyltransferase related to clostridial glucosylating toxins.,Ost GS, Wirth C, Bogdanovic X, Kao WC, Schorch B, Aktories PJK, Papatheodorou P, Schwan C, Schlosser A, Jank T, Hunte C, Aktories K Sci Adv. 2020 Mar 11;6(11):eaaz2094. doi: 10.1126/sciadv.aaz2094. eCollection, 2020 Mar. PMID:32195351^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.