1. Convergent vews on disordered protein dynamics from NMR and computational approaches
- Author
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Nicola, Salvi, Vojtěch, Zapletal, Zuzana, Jaseňáková, Milan, Zachrdla, Petr, Padrta, Subhash, Narasimhan, Thorsten, Marquardsen, Jean-Max, Tyburn, Lukáš, Žídek, Martin, Blackledge, Fabien, Ferrage, Pavel, Kadeřávek, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Masaryk University [Brno] (MUNI), Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bruker BioSpin MRI GmbH [Ettlingen, Germany], ANR-18-CE29-0003,NANO-DISPRO,Une méthode intégrative pour déterminer les mouvements nanométriques des protéines désordonnées(2018), Ferrage, Fabien, and APPEL À PROJETS GÉNÉRIQUE 2018 - Une méthode intégrative pour déterminer les mouvements nanométriques des protéines désordonnées - - NANO-DISPRO2018 - ANR-18-CE29-0003 - AAPG2018 - VALID
- Subjects
Intrinsically Disordered Proteins ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics ,[CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry ,Magnetic Resonance Spectroscopy ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,Protein Conformation ,[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,Biophysics ,[SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics ,DNA-Directed RNA Polymerases ,Molecular Dynamics Simulation ,Amides - Abstract
International audience; Intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs) is a class of biologically important proteins exhibiting specific biophysical characteristics. They lack a hydrophobic core, and their conformational behavior is strongly influenced by electrostatic interactions. IDPs and IDRs are highly dynamic, and a characterization of the motions of IDPs and IDRs is essential for their physically correct description. NMR together with molecular dynamics simulations are the methods best suited to such a task because they provide information about dynamics of proteins with atomistic resolution. Here, we present a study of motions of a disordered C-terminal domain of the delta subunit of RNA polymerase from Bacillus subtilis. Positively and negatively charged residues in the studied domain form transient electrostatic contacts critical for the biological function. Our study is focused on investigation of ps-ns dynamics of backbone of the delta subunit based on analysis of amide 15N NMR relaxation data and molecular dynamics simulations. In order to extend an informational content of NMR data to lower frequencies, which are more sensitive to slower motions, we combined standard (high-field) NMR relaxation experiments with high-resolution relaxometry. Altogether, we collected data reporting the relaxation at 12 different magnetic fields, resulting in an unprecedented data set. Our results document that the analysis of such data provides a consistent description of dynamics and confirms the validity of so far used protocols of the analysis of dynamics of IDPs also for a partially folded protein. In addition, the potential to access detailed description of motions at the timescale of tens of ns with the help of relaxometry data is discussed. Interestingly, in our case, it appears to be mostly relevant for a region involved in the formation of temporary contacts within the disordered region, which was previously proven to be biologically important.
- Published
- 2022
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