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E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis
Author(s) -
Pruneda Jonathan N,
Smith F Donelson,
Daurie Angela,
Swaney Danielle L,
Villén Judit,
Scott John D,
Stadnyk Andrew W,
Le Trong Isolde,
Stenkamp Ronald E,
Klevit Rachel E,
Rohde John R,
Brzovic Peter S
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/embj.201386386
Subject(s) - biology , effector , shigella , pathogenesis , microbiology and biotechnology , shigella flexneri , kinase , virology , immunology , genetics , gene , escherichia coli
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.