5w60 | pdb_00005w60
Crystal structure of BAXP168G monomer cryo-protected with ethylene glycol
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 PubMedBAX and BAK are essential mediators of intrinsic apoptosis that permeabilize the mitochondrial outer membrane. BAX activation requires its translocation from cytosol to mitochondria where conformational changes cause its oligomerization. To better understand the critical step of translocation, we examined its blockade by mutation near the C terminus (P168G) or by antibody binding near the N terminus. Similarities in the crystal structures of wild-type and BAX P168G but significant other differences suggest that cytosolic BAX exists as an ensemble of conformers, and that the distribution of conformers within the ensemble determines the different functions of wild-type and mutant proteins. We also describe the structure of BAX in complex with an antibody, 3C10, that inhibits cytosolic BAX by limiting exposure of the membrane-associating helix alpha9, as does the P168G mutation. Our data for both means of BAX inhibition argue for an allosteric model of BAX regulation that derives from properties of the ensemble of conformers. Ensemble Properties of Bax Determine Its Function.,Robin AY, Iyer S, Birkinshaw RW, Sandow J, Wardak A, Luo CS, Shi M, Webb AI, Czabotar PE, Kluck RM, Colman PM Structure. 2018 Aug 4. pii: S0969-2126(18)30252-1. doi:, 10.1016/j.str.2018.07.006. PMID:30122452[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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