4ZIE

Crystal Structure of core/latch dimer of Bax in complex with BimBH3

Summary for 4ZIE

• Entry DOI: 10.2210/pdb4zie/pdb
• Related: 4ZIF 4ZIG 4ZIH 4ZII
• Descriptor: Apoptosis regulator BAX, Bcl-2-like protein 11, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: bax, apoptosis, bh3 domain, structural genomics
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 21848.75

Authors

Krishna Kumar, K.,Robin, A.Y.,Westphal, D.,Wardak, A.Z.,Thompson, G.V.,Dewson, G.,Colman, P.M.,Czabotar, P.E. (deposition date: 2015-04-28, release date: 2015-07-22, Last modification date: 2023-09-27)

Primary citation

Robin, A.Y.,Krishna Kumar, K.,Westphal, D.,Wardak, A.Z.,Thompson, G.V.,Dewson, G.,Colman, P.M.,Czabotar, P.E.
Crystal structure of Bax bound to the BH3 peptide of Bim identifies important contacts for interaction.
Cell Death Dis, 6:e1809-e1809, 2015

PubMed 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 BaxΔC26 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 BaxΔC21, the structure of the BimBH3 complex with BaxΔC displays a cavity surrounded by Bax α1, α2, α5 and α8. Our results are consistent with a model in which binding of an activator BH3 domain to the Bax groove initiates separation of its core (α2-α5) and latch (α6-α8) domains, enabling its subsequent dimerisation and the permeabilisation of the mitochondrial outer membrane.

PubMed: 26158515
DOI: 10.1038/cddis.2015.141

Experimental method

X-RAY DIFFRACTION (1.797 Å)