Complex structure of OspI and Ubc13: the molecular basis of Ubc13 deamidation and convergence of bacterial and host E2 recognition

Ubc13 is an important ubiquitin-conjugating (E2) enzyme in the NF-κB signaling pathway. The Shigella effector OspI targets Ubc13 and deamidates Gln100 of Ubc13 to a glutamic acid residue, leading to the inhibition of host inflammatory responses. Here we report the crystal structure of the OspI-Ubc13...

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Bibliographic Details
Published in:PLoS pathogens 2013-04, Vol.9 (4), p.e1003322-e1003322
Main Authors: Fu, Panhan, Zhang, Xiaoqing, Jin, Mengmeng, Xu, Li, Wang, Chong, Xia, Zongping, Zhu, Yongqun
Format: Article
Language:English
Subjects:
Amidohydrolases - chemistry
Amidohydrolases - metabolism
Amino Acid Sequence
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Bacterial Secretion Systems
Binding sites
Binding Sites - genetics
Biology
Chemical bonds
Convergence
Crystal structure
Crystallography, X-Ray
Enzymes
HEK293 Cells
Humans
Inflammation - immunology
Inflammation - microbiology
Kinases
Multiprotein Complexes - chemistry
Multiprotein Complexes - metabolism
NF-kappa B - metabolism
Phosphorylation
Protein Binding - genetics
Proteins
Sequence Alignment
Shigella flexneri - immunology
Shigella flexneri - metabolism
TNF Receptor-Associated Factor 6 - metabolism
Ubiquitin-Conjugating Enzymes - chemistry
Ubiquitin-Conjugating Enzymes - metabolism
Ubiquitination
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Summary:Ubc13 is an important ubiquitin-conjugating (E2) enzyme in the NF-κB signaling pathway. The Shigella effector OspI targets Ubc13 and deamidates Gln100 of Ubc13 to a glutamic acid residue, leading to the inhibition of host inflammatory responses. Here we report the crystal structure of the OspI-Ubc13 complex at 2.3 Å resolution. The structure reveals that OspI uses two differently charged regions to extensively interact with the α1 helix, L1 loop and L2 loop of Ubc13. The Gln100 residue is bound within the hydrophilic catalytic pocket of OspI. A comparison between Ubc13-bound and wild-type free OspI structures revealed that Ubc13 binding induces notable structural reassembly of the catalytic pocket, suggesting that substrate binding might be involved in the catalysis of OspI. The OspI-binding sites in Ubc13 largely overlap with the binding residues for host ubiquitin E3 ligases and a deubiquitinating enzyme, which suggests that the bacterial effector and host proteins exploit the same surface on Ubc13 for specific recognition. Biochemical results indicate that both of the differently charged regions in OspI are important for the interaction with Ubc13, and the specificity determinants in Ubc13 for OspI recognition reside in the distinct residues in the α1 helix and L2 region. Our study reveals the molecular basis of Ubc13 deamidation by OspI, as well as a convergence of E2 recognition by bacterial and host proteins.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1003322