4cim

Complex of a Bcl-w BH3 mutant with a BH3 domain

spinqualitylabelsall models 4cim, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4cim is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B2CL2_HUMAN Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX. Publication Abstract from PubMed Bcl-2 Homology 3 (BH3) domains are short sequence motifs that mediate nearly all protein-protein interactions between B cell lymphoma 2 (Bcl-2) family proteins in the intrinsic apoptotic cell death pathway. These sequences are found on both pro-survival and pro-apoptotic members even though their primary function is believed to be associated with induction of cell death. Here, we identify critical features of the BH3 domains of pro-survival proteins that distinguish them functionally from their pro-apoptotic counterparts. Biochemical and X-ray crystallographic studies demonstrate that these differences reduce the capacity of most pro-survival proteins to form high affinity "BH3-in-groove" complexes that are critical for cell death induction. Switching these residues for the corresponding residues in Bcl-2 homologous antagonist/killer (Bak) increases the binding affinity of isolated BH3 domains to pro-survival proteins, however, their exchange in the context of the parental protein causes rapid proteasomal degradation due to protein destabilization. This is supported by further X-ray crystallographic studies that capture elements of this destabilization in one pro-survival protein, Bcl-w. In pro-apoptotic Bak, we demonstrate that the corresponding distinguishing residues are important for its stability, cell-killing capacity, and antagonism by pro-survival proteins. The Functional Differences of Pro-survival and Pro-apoptotic B cell lymphoma 2 (Bcl-2) Proteins Depend on Structural Differences in their Bcl-2 Homology 3 (BH3) Domains.,Lee EF, Dewson G, Evangelista M, Pettikiriarachchi A, Zhu H, Colman PM, Fairlie WD J Biol Chem. 2014 Nov 3. pii: jbc.M114.610758. PMID:25371206 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also B-cell lymphoma proteins 3D structures

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