title: Redefining the BH3 Death Domain as a 'Short Linear Motif'.
abstract: B cell lymphoma-2 (BCL-2)-related proteins control programmed cell death through a complex network of protein-protein interactions mediated by BCL-2 homology 3 (BH3) domains. Given their roles as dynamic linchpins, the discovery of novel BH3-containing proteins has attracted considerable attention. However, without a clearly defined BH3 signature sequence the BCL-2 family has expanded to include a nebulous group of nonhomologous BH3-only proteins, now justified by an intriguing twist. We present evidence that BH3s from both ordered and disordered proteins represent a new class of short linear motifs (SLiMs) or molecular recognition features (MoRFs) and are diverse in their evolutionary histories. The implied corollaries are that BH3s have a broad phylogenetic distribution and could potentially bind to non-BCL-2-like structural domains with distinct functions.
authors.affiliation: Molecular Biology of the Cell Laboratory, Ecole Normale Supérieure de Lyon, UMR 5239, CNRS-UCBL-ENS Lyon, 46 Allée d'Italie, 69364 Lyon cedex 07, France. Electronic address: abdel.aouacheria@ens-lyon.fr.
authors.forename: Abdel
authors.initials: A
authors.lastname: Aouacheria
authors.affiliation: Bases Moléculaires et Structurales des Systèmes Infectieux, UMR 5086, CNRS, Université Lyon 1, IBCP - 7 passage du Vercors, 69367 Lyon cedex 07, France; Centre de Recherche en Cancérologie de Lyon, UMR INSERM U1052, CNRS 5286, Centre Léon Bérard, Université Lyon 1, 151 cours Albert Thomas, 69424 Lyon cedex 03, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Combet
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest 1117, Hungary; VIB Structural Biology Research Center (SBRC), Vrije Universiteit Brussel, Brussels 1050, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Tompa
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA. Electronic address: hardwick@jhu.edu.
authors.forename: J Marie
authors.initials: JM
authors.lastname: Hardwick
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein
keywords: BCL-2 family; BH3; MoRF/MoRE; SLiM; globular domains; intrinsically disordered proteins