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Contents 1 BAX Protein 2 Abstract 3 Reference 4 Reference

BAX Protein

Abstract

spinqualitylabelsall models PDB ID 1f16 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
1f16, 20 NMR models ()
Structural annotation: Resources: CATH : 1F16A00 InterPro : Ipr012238, Ipr000712, Ipr002475 Pfam : PF00452 SCOP : d1f16a_ UniProt : Q07812
Functional annotation: Cellular component: membrane integral to membrane mitochondrion cytosol Biological process: regulation of protein heterodimerization activity negative regulation of cell cycle positive regulation of neuron apoptosis regulation of apoptosis regulation of protein homodimerization activity apoptosis cell cycle caspase activation induction of apoptosis Molecular function: protein heterodimerization activity protein homodimerization activity protein binding
Evolutionary conservation: Toggle Conservation Colors: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha-helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB-BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.

Reference

• Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science. 1996 Nov 8;274(5289):948-53. PMID:8875929

Reference

Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu HC, Kim H, Cheng EH, Tjandra N, Walensky LDBAX activation is initiated at a novel interaction siteNature v455, p.1076-1081

structure obtained by: BAX activation is initiated at a novel interaction site. Gavathiotis, E., Suzuki, M., Davis, M.L., Pitter, K., Bird, G.H., Katz, S.G., Tu, H.C., Kim, H., Cheng, E.H., Tjandra, N., Walensky, L.D.(2008) Nature 455: 1076-1081