Crystal structure of Bax bound to the BH3 peptide of Bim identifies important contacts for interaction
Journal Title
Cell Death Dis
Publication Type
Journal Article
The BH3-only protein Bim is a potent direct activator of the proapoptotic effector protein Bax, but the structural basis for its activity has remained poorly defined. Here we describe the crystal structure of the BimBH3 peptide bound to BaxDeltaC26 and structure-based mutagenesis studies. Similar to BidBH3, the BimBH3 peptide binds into the cognate surface groove of Bax using the conserved hydrophobic BH3 residues h1-h4. However, the structure and mutagenesis data show that Bim is less reliant compared with Bid on its 'h0' residues for activating Bax and that a single amino-acid difference between Bim and Bid encodes a fivefold difference in Bax-binding potency. Similar to the structures of BidBH3 and BaxBH3 bound to BaxDeltaC21, the structure of the BimBH3 complex with BaxDeltaC displays a cavity surrounded by Bax alpha1, alpha2, alpha5 and alpha8. Our results are consistent with a model in which binding of an activator BH3 domain to the Bax groove initiates separation of its core (alpha2-alpha5) and latch (alpha6-alpha8) domains, enabling its subsequent dimerisation and the permeabilisation of the mitochondrial outer membrane.
WEHI Research Division(s)
Structural Biology; Cell Signalling And Cell Death
PubMed ID
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Creation Date: 2015-07-15 02:16:02
Last Modified: 2015-07-15 02:38:55
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