4b4s
From Proteopedia
Crystal Structure of a pro-survival Bcl-2:Bim BH3 complex
Structural highlights
Function[B2L10_HUMAN] Promotes cell survival. Suppresses apoptosis induced by BAX but not BAK.[1] [B2L11_HUMAN] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.[2] [3] [4] [5] [6] [7] Publication Abstract from PubMedB-cell lymphoma-2 (Bcl-2) proteins mediate intrinsic-, or mitochondrial-, initiated apoptosis. We have investigated the structure and function of the least characterized Bcl-2 family member, Bcl-B, solving the crystal structure of a Bcl-B:Bim complex to 1.9 A resolution. Bcl-B is distinguished from other Bcl-2 family members through an insertion of an unstructured loop between helices alpha5 and alpha6. Probing Bcl-B interactions with Bcl-2 homology (BH)3 motifs using a combination of biophysical- and cell-based assays revealed a unique BH3-only protein binding profile. Bcl-B has high-affinity interactions with Bim and Bik only. Our results not only delineate the mode of action of Bcl-B but also complete our understanding of the specific interactions between BH3-only proteins and their prosurvival Bcl-2 counterparts. Notably, we conclude that Bim is the universal prosurvival antagonist as no other BH3-only protein binds all six prosurvival proteins and that Mcl-1 and Bcl-x(L) form a distinct prosurvival dyad. The restricted binding repertoire of Bcl-B leaves Bim as the universal BH3-only prosurvival Bcl-2 protein antagonist.,Rautureau GJ, Yabal M, Yang H, Huang DC, Kvansakul M, Hinds MG Cell Death Dis. 2012 Dec 13;3:e443. doi: 10.1038/cddis.2012.178. PMID:23235460[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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