Journal article
Crystal structure of Bax bound to the BH3 peptide of Bim identifies important contacts for interaction
AY Robin, K Krishna Kumar, D Westphal, AZ Wardak, GV Thompson, G Dewson, PM Colman, PE Czabotar
Cell Death and Disease | NATURE PUBLISHING GROUP | Published : 2015
Abstract
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 BaxAC26 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 BidB..
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Awarded by Australian Research Council
Funding Acknowledgements
We thank Ruth Kluck and Jerry Adams for discussions and comments on the manuscript and the beamline staff at the Australian Synchrotron where diffraction data were collected. Crystallisation experiments were performed at the Bio21 C3 Collaborative Crystallisation Centre. PEC and PMC acknowledge NHMRC Fellowships, GD acknowledges an ARC Future Fellowship and DW acknowledges a DFG Postdoctoral Fellowship. Our work is supported by the NHMRC (Australia; Projects Grants 1079706, 1059331 and 1023055 and Program Grant 1016701), the Australian Cancer Research Foundation, the Leukemia and Lymphoma Society (US), the Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC IRIISS.