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

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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Rautureau GJ,Yabal M,Yang H,Huang DC,Kvansakul M,Hinds MG

doi

10.1038/cddis.2012.178

subject

Has Abstract

pub_date

2012-12-13 00:00:00

pages

e443

issn

2041-4889

pii

cddis2012178

journal_volume

3

pub_type

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