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 language | English (US) |
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Pages (from-to) | 437-449 |
Number of pages | 13 |
Journal | EMBO Journal |
Volume | 33 |
Issue number | 5 |
DOIs | |
State | Published - Mar 3 2014 |
Externally published | Yes |
Keywords
- E2 Ub-conjugating enzyme
- Shigella
- bacterial effector
- kinase
- ubiquitin
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology