4zih
From Proteopedia
Crystal Structure of core/latch dimer of Bax in complex with BimBH3mini
Structural highlights
FunctionBAX_HUMAN Accelerates programmed cell death by binding to, and antagonizing the apoptosis repressor BCL2 or its adenovirus homolog E1B 19k protein. Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe BH3-only protein Bim is a potent direct activator of the proapoptotic effector protein Bax, but the structural basis for its activity has remained poorly defined. Here we describe the crystal structure of the BimBH3 peptide bound to BaxDeltaC26 and structure-based mutagenesis studies. Similar to BidBH3, the BimBH3 peptide binds into the cognate surface groove of Bax using the conserved hydrophobic BH3 residues h1-h4. However, the structure and mutagenesis data show that Bim is less reliant compared with Bid on its 'h0' residues for activating Bax and that a single amino-acid difference between Bim and Bid encodes a fivefold difference in Bax-binding potency. Similar to the structures of BidBH3 and BaxBH3 bound to BaxDeltaC21, the structure of the BimBH3 complex with BaxDeltaC displays a cavity surrounded by Bax alpha1, alpha2, alpha5 and alpha8. Our results are consistent with a model in which binding of an activator BH3 domain to the Bax groove initiates separation of its core (alpha2-alpha5) and latch (alpha6-alpha8) domains, enabling its subsequent dimerisation and the permeabilisation of the mitochondrial outer membrane. Crystal structure of Bax bound to the BH3 peptide of Bim identifies important contacts for interaction.,Robin AY, Krishna Kumar K, Westphal D, Wardak AZ, Thompson GV, Dewson G, Colman PM, Czabotar PE Cell Death Dis. 2015 Jul 9;6:e1809. doi: 10.1038/cddis.2015.141. PMID:26158515[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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