6lhd
From Proteopedia
Crystal structure of p53/BCL-xL fusion complex
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 PubMedThe tumor suppressor p53 is mutated in approximately half of all human cancers. p53 can induce apoptosis through mitochondrial membrane permeabilization by interacting with and antagonizing the anti-apoptotic proteins BCL-xL and BCL-2. However, the mechanisms by which p53 induces mitochondrial apoptosis remain elusive. Here, we report a 2.5 A crystal structure of human p53/BCL-xL complex. In this structure, two p53 molecules interact as a homodimer, and bind one BCL-xL molecule to form a ternary complex with a 2:1 stoichiometry. Mutations at the p53 dimer interface or p53/BCL-xL interface disrupt p53/BCL-xL interaction and p53-mediated apoptosis. Overall, our current findings of the bona fide structure of p53/BCL-xL complex reveal the molecular basis of the interaction between p53 and BCL-xL, and provide insight into p53-mediated mitochondrial apoptosis. Structural insight into the molecular mechanism of p53-mediated mitochondrial apoptosis.,Wei H, Qu L, Dai S, Li Y, Wang H, Feng Y, Chen X, Jiang L, Guo M, Li J, Chen Z, Chen L, Zhang Y, Chen Y Nat Commun. 2021 Apr 16;12(1):2280. doi: 10.1038/s41467-021-22655-6. PMID:33863900[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Chen, Y | Wei, H | Complex | Interaction | Protein binding
