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Title: E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis

Pathogenic bacteria introduce effector proteins directly into the cytosol of eukaryotic cells to promote invasion and colonization. OspG, a Shigella spp. effector kinase, plays a role in this process by helping to suppress the host inflammatory response. OspG has been reported to bind host E2 ubiquitin-conjugating enzymes activated with ubiquitin (E2~Ub), a key enzyme complex in ubiquitin transfer pathways. A cocrystal structure of the OspG/UbcH5c~Ub complex reveals that complex formation has important ramifications for the activity of both OspG and the UbcH5c~Ub conjugate. OspG is a minimal kinase domain containing only essential elements required for catalysis. UbcH5c~Ub binding stabilizes an active conformation of the kinase, greatly enhancing OspG kinase activity. In contrast, interaction with OspG stabilizes an extended, less reactive form of UbcH5c~Ub. Recognizing conserved E2 features, OspG can interact with at least ten distinct human E2s~Ub. Mouse oral infection studies indicate that E2~Ub conjugates act as novel regulators of OspG effector kinase function in eukaryotic host cells.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [4] ;  [2] ;  [5] ;  [6] ;  [7] ;  [1] ;  [3] ;  [1]
  1. Department of Biochemistry, University of Washington, Seattle WA USA
  2. Howard Hughes Medical Institute, Department of Pharmacology, University of Washington, Seattle WA USA
  3. Department of Microbiology and Immunology, Dalhousie University, Halifax NS Canada
  4. Department of Genome Sciences, University of Washington, Seattle WA USA
  5. Department of Pediatrics, Dalhousie University, Halifax NS Canada
  6. Department of Biological Structure, University of Washington, Seattle WA USA
  7. Department of Biochemistry, University of Washington, Seattle WA USA; Department of Biological Structure, University of Washington, Seattle WA USA
Publication Date:
OSTI Identifier:
1227064
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: EMBO Journal; Journal Volume: 33; Journal Issue: 5
Research Org:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES Environmental Molecular Sciences Laboratory