4Q5E

Shigella Effector Kinase OspG bound to E2-Ub UbcH7-Ub Conjugate

Summary for 4Q5E

• Entry DOI: 10.2210/pdb4q5e/pdb
• Related: 4Q5H
• Descriptor: Protein kinase OspG, Polyubiquitin, Ubiquitin-conjugating enzyme E2 L3, ... (4 entities in total)
• Functional Keywords: protein-protein complex, structural genomics, montreal-kingston bacterial structural genomics initiative, bsgi, kinase fold, inhibition of nf-kb pathway, unknown function, protein binding
• Biological source: Shigella sonnei Ss046; More
• Cellular location: Secreted : Q3YTH2; Cytoplasm : P0CG63; Nucleus : P68036
• Total number of polymer chains: 3
• Total formula weight: 46812.08

Authors

Cygler, M.,Grishin, A.M.,Montreal-Kingston Bacterial Structural Genomics Initiative (BSGI) (deposition date: 2014-04-16, release date: 2014-07-02, Last modification date: 2024-10-30)

Primary citation

Grishin, A.M.,Condos, T.E.,Barber, K.R.,Campbell-Valois, F.X.,Parsot, C.,Shaw, G.S.,Cygler, M.
Structural Basis for the Inhibition of Host Protein Ubiquitination by Shigella Effector Kinase OspG.
Structure, 22:878-888, 2014

PubMed Abstract: Shigella invasion of its human host is assisted by T3SS-delivered effector proteins. The OspG effector kinase binds ubiquitin and ubiquitin-loaded E2-conjugating enzymes, including UbcH5b and UbcH7, and attenuates the host innate immune NF-kB signaling. We present the structure of OspG bound to the UbcH7∼Ub conjugate. OspG has a minimal kinase fold lacking the activation loop of regulatory kinases. UbcH7∼Ub binds OspG at sites remote from the kinase active site, yet increases its kinase activity. The ubiquitin is positioned in the "open" conformation with respect to UbcH7 using its I44 patch to interact with the C terminus of OspG. UbcH7 binds to OspG using two conserved loops essential for E3 ligase recruitment. The interaction of the UbcH7∼Ub with OspG is remarkably similar to the interaction of an E2∼Ub with a HECT E3 ligase. OspG interferes with the interaction of UbcH7 with the E3 parkin and inhibits the activity of the E3.

PubMed: 24856362
DOI: 10.1016/j.str.2014.04.010

Experimental method

X-RAY DIFFRACTION (1.869 Å)