4s0p | pdb_00004s0p
Crystal Structure of the Autoinhibited Dimer of Pro-apoptotic BAX (II)
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 PubMedPro-apoptotic BAX is a cell fate regulator playing an important role in cellular homeostasis and pathological cell death. BAX is predominantly localized in the cytosol, where it has a quiescent monomer conformation. Following a pro-apoptotic trigger, cytosolic BAX is activated and translocates to the mitochondria to initiate mitochondrial dysfunction and apoptosis. Here, cellular, biochemical, and structural data unexpectedly demonstrate that cytosolic BAX also has an inactive dimer conformation that regulates its activation. The full-length crystal structure of the inactive BAX dimer revealed an asymmetric interaction consistent with inhibition of the N-terminal conformational change of one protomer and the displacement of the C-terminal helix alpha9 of the second protomer. This autoinhibited BAX dimer dissociates to BAX monomers before BAX can be activated. Our data support a model whereby the degree of apoptosis induction is regulated by the conformation of cytosolic BAX and identify an unprecedented mechanism of cytosolic BAX inhibition. An Autoinhibited Dimeric Form of BAX Regulates the BAX Activation Pathway.,Garner TP, Reyna DE, Priyadarshi A, Chen HC, Li S, Wu Y, Ganesan YT, Malashkevich VN, Almo SS, Cheng EH, Gavathiotis E Mol Cell. 2016 Aug 4;63(3):485-97. doi: 10.1016/j.molcel.2016.06.010. Epub 2016, Jul 14. PMID:27425408[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||
