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Fragment-Based NMR Study of the Conformational Dynamics in the bHLH Transcription Factor Ascl1.
Baronti, Lorenzo; Hosek, Tomás; Gil-Caballero, Sergio; Raveh-Amit, Hadas; Calçada, Eduardo O; Ayala, Isabel; Dinnyés, András; Felli, Isabella C; Pierattelli, Roberta; Brutscher, Bernhard.
Afiliação
  • Baronti L; BioTalentum Ltd., Gödöllo, Hungary.
  • Hosek T; Institut de Biologie Structurale, Université Grenoble, Grenoble, France; Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Grenoble, France; Centre National de la Recherche Scientifique (CNRS), Grenoble, France.
  • Gil-Caballero S; Institut de Biologie Structurale, Université Grenoble, Grenoble, France; Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Grenoble, France; Centre National de la Recherche Scientifique (CNRS), Grenoble, France.
  • Raveh-Amit H; BioTalentum Ltd., Gödöllo, Hungary.
  • Calçada EO; Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy.
  • Ayala I; Institut de Biologie Structurale, Université Grenoble, Grenoble, France; Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Grenoble, France; Centre National de la Recherche Scientifique (CNRS), Grenoble, France.
  • Dinnyés A; BioTalentum Ltd., Gödöllo, Hungary.
  • Felli IC; Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy. Electronic address: felli@cerm.unifi.it.
  • Pierattelli R; Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy; Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy. Electronic address: pierattelli@cerm.unifi.it.
  • Brutscher B; Institut de Biologie Structurale, Université Grenoble, Grenoble, France; Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Grenoble, France; Centre National de la Recherche Scientifique (CNRS), Grenoble, France. Electronic address: bernhard.brutscher@ibs.fr.
Biophys J ; 112(7): 1366-1373, 2017 Apr 11.
Article em En | MEDLINE | ID: mdl-28402879
ABSTRACT
The Achaete-scute homolog 1 (Ascl1) protein regulates a large subset of genes that leads neuronal progenitor cells to distinctive differentiation pathways during human brain development. Although it is well known that Ascl1 binds DNA as a homo- or heterodimer via its basic helix-loop-helix (bHLH) motif, little is known about the conformational sampling properties of the DNA-free full-length protein, and in particular about the bHLH domain-flanking N- and C-terminal segments, which are predicted to be highly disordered in solution. The structural heterogeneity, low solubility, and high aggregation propensity of Ascl1 in aqueous buffer solutions make high-resolution studies of this protein a challenging task. Here, we have adopted a fragment-based strategy that allowed us to obtain high-quality NMR data providing, to our knowledge, the first comprehensive high-resolution information on the structural propensities and conformational dynamics of Ascl1. The emerging picture is that of an overall extended and highly dynamic polypeptide chain comprising three helical segments and lacking persistent long-range interactions. We also show that the C-terminal helix of the bHLH domain is involved in intermolecular interactions, even in the absence of DNA. Our results contribute to a better understanding of the mechanisms of action that govern the regulation of proneural transcription factors.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espectroscopia de Ressonância Magnética / Fatores de Transcrição Hélice-Alça-Hélice Básicos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Biophys J Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Hungria

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espectroscopia de Ressonância Magnética / Fatores de Transcrição Hélice-Alça-Hélice Básicos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Biophys J Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Hungria