1jd4
Crystal Structure of DIAP1-BIR2Crystal Structure of DIAP1-BIR2
Structural highlights
FunctionDIAP1_DROME Anti-apoptotic protein which functions as a caspase regulator, using its E3 ubiquitin-protein ligase activity to smother caspase activity. Binds, ubiquitinates and inactivates initiator caspase Dronc, and effector caspases Drice and Dcp-1. Acts as a Nedd8-E3 ubiquitin-protein ligase for Drice. Suppresses apoptosis by targeting the apoptosome for ubiquitination and inactivation. Plays an important role in cell motility. Overexpression suppresses rpr and hid-dependent cell death in the eye. Interaction of Diap1 with Dronc is required to suppress Dronc-mediated cell death through Diap1-mediated ubiquitination of Dronc. Acts as a positive regulator of Wnt signaling.[1] [2] [3] [4] [5] [6] 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 PubMedThe inhibitor of apoptosis protein DIAP1 suppresses apoptosis in Drosophila, with the second BIR domain (BIR2) playing an important role. Three proteins, Hid, Grim, and Reaper, promote apoptosis, in part by binding to DIAP1 through their conserved N-terminal sequences. The crystal structures of DIAP1-BIR2 by itself and in complex with the N-terminal peptides from Hid and Grim reveal that these peptides bind a surface groove on DIAP1, with the first four amino acids mimicking the binding of the Smac tetrapeptide to XIAP. The next 3 residues also contribute to binding through hydrophobic interactions. Interestingly, peptide binding induces the formation of an additional alpha helix in DIAP1. Our study reveals the structural conservation and diversity necessary for the binding of IAPs by the Drosophila Hid/Grim/Reaper and the mammalian Smac proteins. Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides.,Wu JW, Cocina AE, Chai J, Hay BA, Shi Y Mol Cell. 2001 Jul;8(1):95-104. PMID:11511363[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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