3r85 | pdb_00003r85
Crystal structure of human SOUL BH3 domain in complex with Bcl-xL
Structural highlights
Function[B2CL1_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.[1] [2] Isoform Bcl-X(S) promotes apoptosis.[3] [4] [HEBP2_HUMAN] Can promote mitochondrial permeability transition and facilitate necrotic cell death under different types of stress conditions. Does not bind hemin.[5] Publication Abstract from PubMedThe SOUL protein is known to induce apoptosis by provoking the mitochondrial permeability transition and a sequence homologous to the Bcl-2 homology 3 (BH3) domains has been recently identified in it thus making it a potential new member of the BH3-only protein family. Here we present NMR, SPR and crystallographic evidence that a peptide spanning SOUL residues 147 - 172 interacts with the anti-apoptotic protein Bcl-xL. We have crystallized SOUL alone and the complex of its BH3 domain peptide with Bcl-xL and solved their three-dimensional structures. The SOUL monomer is a single domain organized as a distorted beta barrel with eight anti-parallel strands and two alpha helices. The BH3 domain extends across 15 residues at the end of the second helix and 8 amino acids in the chain following it. There are important structural differences in the BH3 domain in the intact SOUL molecule and the same sequence bound to Bcl-xL. Structural changes in the BH3 domain of SOUL protein upon interaction with the anti-apoptotic protein Bcl-xL.,Ambrosi E, Capaldi S, Bovi M, Saccomani G, Perduca M, Monaco HL Biochem J. 2011 Jun 6. PMID:21639858[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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