E2∼Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis

Jonathan N. Pruneda, F. Donelson Smith, Angela Daurie, Danielle L. Swaney, Judit Villén, John D. Scott, Andrew W. Stadnyk, Isolde Le Trong, Ronald E. Stenkamp, Rachel E. Klevit, John R. Rohde, Peter S. Brzovic

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

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 co-crystal 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.

Original languageEnglish (US)
Pages (from-to)437-449
Number of pages13
JournalEMBO Journal
Volume33
Issue number5
DOIs
StatePublished - Mar 3 2014

Keywords

  • E2 Ub-conjugating enzyme
  • Shigella
  • bacterial effector
  • kinase
  • ubiquitin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'E2∼Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis'. Together they form a unique fingerprint.

  • Cite this

    Pruneda, J. N., Smith, F. D., Daurie, A., Swaney, D. L., Villén, J., Scott, J. D., Stadnyk, A. W., Le Trong, I., Stenkamp, R. E., Klevit, R. E., Rohde, J. R., & Brzovic, P. S. (2014). E2∼Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis. EMBO Journal, 33(5), 437-449. https://doi.org/10.1002/embj.201386386