title: The structural biology of BH3-only proteins.
abstract: B-cell lymphoma-2 (Bcl-2) homology-3 (BH3)-only proteins are considered members of the Bcl-2 family, though they bear little sequence or structural identity with the multi-BH motif prosurvival or proapoptotic Bcl-2 proteins like Bcl-2 or Bax. They are better considered a separate phylogenetic entity. In combination, results from biophysical, biochemical, cell biological, and animal studies in conjunction with structural investigations have elucidated the function and mechanism of action of these proteins. Either by antagonizing prosurvival Bcl-2 proteins or directly activating proapoptotic Bcl-2 proteins (Bax or Bak) they initiate apoptosis. BH3-only proteins are intrinsically disordered and fold and bind into a groove provided by their cognate receptor Bcl-2 family proteins. Our detailed molecular understanding of BH3-only protein action has aided the development of novel chemical entities that initiate cell death by mimicking the properties of BH3-only proteins.
authors: La Trobe Institute for Medical Science, La Trobe University, Bundoora, Victoria, Australia. Electronic address: m.kvansakul@latrobe.edu.au.
authors: Marc
authors: M
authors: Kvansakul
authors: School of Chemistry, The University of Melbourne, Parkville, Victoria, Australia; Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: mhinds@unimelb.edu.au.
authors: Mark G
authors: MG
authors: Hinds
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods; D060066:Protein Interaction Maps; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Apoptosis; BH3-only; Bcl-2; Cancer; Protein structure