Inverse control of Rab proteins by Yersinia ADP-ribosyltransferase and glycosyltransferase related to clostridial glucosylating toxins

Sci Adv. 2020 Mar 11;6(11):eaaz2094. doi: 10.1126/sciadv.aaz2094. eCollection 2020 Mar.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP Ribose Transferases* / chemistry
  • ADP Ribose Transferases* / metabolism
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / metabolism
  • Bacterial Toxins* / chemistry
  • Bacterial Toxins* / metabolism
  • Crystallography, X-Ray
  • Glucosyltransferases / chemistry
  • Glucosyltransferases / metabolism
  • Glycosylation
  • Glycosyltransferases* / chemistry
  • Glycosyltransferases* / metabolism
  • HeLa Cells
  • Humans
  • Protein Domains
  • Uridine Diphosphate / chemistry
  • Uridine Diphosphate / metabolism
  • Yersinia* / chemistry
  • Yersinia* / enzymology
  • rab GTP-Binding Proteins / metabolism*
  • rab5 GTP-Binding Proteins / metabolism*


  • Bacterial Proteins
  • Bacterial Toxins
  • RAB31 protein, human
  • Uridine Diphosphate
  • Glycosyltransferases
  • Glucosyltransferases
  • ADP Ribose Transferases
  • RAB5C protein, human
  • rab GTP-Binding Proteins
  • rab5 GTP-Binding Proteins

Supplementary concepts

  • Yersinia mollaretii