Research Publications

Back

The restricted binding repertoire of Bcl-B leaves Bim as the universal BH3-only prosurvival Bcl-2 protein antagonist


Rautureau, GJP; Yabal, M; Yang, H; Huang, DCS; Kvansakul, M; Hinds, MG
2012-12
CELL DEATH & DISEASE
Journal Article
3
e443
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 angstrom resolution. Bcl-B is distinguished from other Bcl-2 family members through an insertion of an unstructured loop between helices alpha 5 and alpha 6. 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. Cell Death and Disease (2012) 3, e443; doi:10.1038/cddis.2012.178; published online 13 December 2012
NATURE PUBLISHING GROUP
APOPTOTIC CELL-DEATH; INDUCE APOPTOSIS; BH3 DOMAINS; FAMILY; MCL-1; BAX; CANCER; INHIBITOR; REGULATOR; HOMOLOG
Chemical Biology
10.1038/cddis.2012.178
Copyright © 2012 Macmillan Publishers Limited This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/