4ppi | pdb_00004ppi
Crystal structure of Bcl-xL hexamer
Structural highlights
Function[B2CL1_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.[1] [2] Isoform Bcl-X(S) promotes apoptosis.[3] [4] Publication Abstract from PubMedBcl-2 family proteins are key regulators for cellular homeostasis in response to apoptotic stimuli. Bcl-xL, an antiapoptotic Bcl-2 family member, undergoes conformational transitions, which leads to two conformational states: the cytoplasmic and membrane-bound. Here we present the crystal and small-angle X-ray scattering (SAXS) structures of Bcl-xL treated with the mild detergent n-Octyl beta-D-Maltoside (OM). The detergent-treated Bcl-xL forms a dimer through three-dimensional domain swapping (3DDS) by swapping helices alpha6-alpha8 between two monomers. Unlike Bax, a proapoptotic member of the Bcl-2 family, Bcl-xL is not converted to 3DDS homodimer upon binding BH3 peptides and ABT-737, a BH3 mimetic drug. We also designed Bcl-xL mutants which cannot dimerize and show that these mutants reduced mitochondrial calcium uptake in MEF cells. This illustrates the structural plasticity in Bcl-xL providing hints toward the probable molecular mechanism for Bcl-xL to play a regulatory role in mitochondrial calcium ion transport. Structural transition in Bcl-xL and its potential association with mitochondrial calcium ion transport.,Rajan S, Choi M, Nguyen QT, Ye H, Liu W, Toh HT, Kang C, Kamariah N, Li C, Huang H, White C, Baek K, Gruber G, Yoon HS Sci Rep. 2015 May 29;5:10609. doi: 10.1038/srep10609. PMID:26023881[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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