4B4S

Crystal Structure of a pro-survival Bcl-2:Bim BH3 complex

Summary for 4B4S

• Entry DOI: 10.2210/pdb4b4s/pdb
• Related: 2V6Q 2VM6 2WH6
• Descriptor: BCL-2-LIKE PROTEIN 10, BCL-2-LIKE PROTEIN 11, TETRAETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: apoptosis
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Mitochondrion: Q9HD36; Endomembrane system; Peripheral membrane protein (By similarity). Isoform BimEL: Mitochondrion. Isoform BimL: Mitochondrion. Isoform BimS: Mitochondrion. Isoform Bim-alpha1: Mitochondrion: O43521
• Total number of polymer chains: 2
• Total formula weight: 23112.09

Authors

Rautureau, G.J.P.,Hinds, M.G.,Kvansakul, M. (deposition date: 2012-08-01, release date: 2013-01-16, Last modification date: 2024-05-08)

Primary citation

Rautureau, G.J.P.,Yabal, M.,Yang, H.,Huang, D.C.S.,Kvansakul, M.,Hinds, M.G.
The Restricted Binding Repertoire of Bcl-B Leaves Bim as the Universal Bh3-Only Prosurvival Bcl-2 Protein Antagonist.
Cell Death Dis., 3:E443-, 2012

PubMed Abstract: B-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 Å resolution. Bcl-B is distinguished from other Bcl-2 family members through an insertion of an unstructured loop between helices α5 and α6. 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.

PubMed: 23235460
DOI: 10.1038/CDDIS.2012.178

Experimental method

X-RAY DIFFRACTION (1.9 Å)