3cvr
Crystal structure of the full length IpaH3
Structural highlights
FunctionIPA3_SHIFL Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is an E3 ubiquitin ligase that interferes with host's ubiquitination pathway. Synthesizes a 'Lys-48'-linked ubiquitin chain, which requires non-covalent binding between ubiquitin and the host ubiquitin-conjugating enzyme UBE2D1.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBacterial pathogens have evolved effector proteins with ubiquitin E3 ligase activities through structural mimicking. Here we report the crystal structure of the Shigella flexneri type III effector IpaH3, a member of the leucine-rich repeat (LRR)-containing bacterial E3 family. The LRR domain is structurally similar to Yersinia pestis YopM and potentially binds to substrates. The structure of the C-terminal E3 domain differs from the typical RING- and HECT-type E3s. IpaH3 synthesizes a Lys48-linked ubiquitin chain, and the reaction requires noncovalent binding between ubiquitin and a specific E2, UbcH5. Free ubiquitin serves as an acceptor for IpaH3-catalyzed ubiquitin transfer. Cys363 within a conserved CXD motif acts as a nucleophile to catalyze ubiquitin transfer through a transthiolation reaction. The D365N mutant is devoid of E3 activities but turns into a potent ubiquitin-E2 thioesterase. Our analysis establishes a structurally and mechanistically distinct class of ubiquitin ligases found exclusively in pathogenic or symbiotic bacteria. Structure of a Shigella effector reveals a new class of ubiquitin ligases.,Zhu Y, Li H, Hu L, Wang J, Zhou Y, Pang Z, Liu L, Shao F Nat Struct Mol Biol. 2008 Dec;15(12):1302-8. Epub 2008 Nov 9. PMID:18997779[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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