PT  - JOURNAL ARTICLE
AU  - Ost, G. Stefan
AU  - Wirth, Christophe
AU  - Bogdanović, Xenia
AU  - Kao, Wei-Chun
AU  - Schorch, Björn
AU  - Aktories, Philipp J. K.
AU  - Papatheodorou, Panagiotis
AU  - Schwan, Carsten
AU  - Schlosser, Andreas
AU  - Jank, Thomas
AU  - Hunte, Carola
AU  - Aktories, Klaus
TI  - Inverse control of Rab proteins by <em>Yersinia</em> ADP-ribosyltransferase and glycosyltransferase related to clostridial glucosylating toxins
AID  - 10.1126/sciadv.aaz2094
DP  - 2020 Mar 01
TA  - Science Advances
PG  - eaaz2094
VI  - 6
IP  - 11
4099  - http://advances.sciencemag.org/content/6/11/eaaz2094.short
4100  - http://advances.sciencemag.org/content/6/11/eaaz2094.full
SO  - Sci Adv2020 Mar 01; 6
AB  - 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 Thr52 and Thr36, respectively, thereby inactivating the Rab proteins. YART ADP-ribosylates Rab5 and Rab31 at Gln79 and Gln64, respectively. This activates Rab proteins by inhibiting GTP hydrolysis. We determined the crystal structure of the glycosyltransferase domain of YGT (YGTG) 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.