In:
Science Advances, American Association for the Advancement of Science (AAAS), Vol. 6, No. 11 ( 2020-03-13)
Abstract:
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-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.
Type of Medium:
Online Resource
ISSN:
2375-2548
DOI:
10.1126/sciadv.aaz2094
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2020
detail.hit.zdb_id:
2810933-8
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