E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis.
EMBO J
; 33(5): 437-49, 2014 Mar 03.
Article
em En
| MEDLINE
| ID: mdl-24446487
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Shigella flexneri
/
Ubiquitina
/
Fatores de Virulência
/
Enzimas de Conjugação de Ubiquitina
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos