title: Interhelical loops within the bHLH domain are determinant in maintaining TWIST1-DNA complexes.
abstract: The basic helix-loop-helix (bHLH) transcription factor TWIST1 is essential to embryonic development, and hijacking of its function contributes to the development of numerous cancer types. It forms either a homodimer or a heterodimeric complex with an E2A or HAND partner. These functionally distinct complexes display sometimes antagonistic functions during development, so that alterations in the balance between them lead to pronounced morphological alterations, as observed in mice and in Saethre-Chotzen syndrome patients. We, here, describe the structures of TWIST1 bHLH-DNA complexes produced in silico through molecular dynamics simulations. We highlight the determinant role of the interhelical loops in maintaining the TWIST1-DNA complex structures and provide a structural explanation for the loss of function associated with several TWIST1 mutations/insertions observed in Saethre-Chotzen syndrome patients. An animated interactive 3D complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:27.
authors.affiliation: a Centre de Recherche en Cancerologie de Lyon , Lyon , F-69000 , France .
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bouard
authors.forename: Raphael
authors.initials: R
authors.lastname: Terreux
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hope
authors.forename: Julie Anne
authors.initials: JA
authors.lastname: Chemelle
authors.forename: Alain
authors.initials: A
authors.lastname: Puisieux
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ansieau
authors.forename: Léa
authors.initials: L
authors.lastname: Payen
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000648:ultrastructure; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051379:Mice; D056004:Molecular Dynamics Simulation; D009154:Mutation; D017570:MyoD Protein / Q000737:chemistry / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D055503:Protein Multimerization; D016415:Sequence Alignment; D058127:Transcription Factor 3 / Q000737:chemistry / Q000648:ultrastructure; D051879:Twist-Related Protein 1 / Q000737:chemistry* / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D017570:MyoD Protein; D009687:Nuclear Proteins; D058127:Transcription Factor 3; D051879:Twist-Related Protein 1; C498765:HAND2 protein, human; C057363:MyoD1 myogenic differentiation protein; C093970:NEUROD1 protein, human; C103173:TWIST1 protein, human; C097341:helix-loop-helix protein, eHAND