Analyzing the Folding and Binding Steps of an Intrinsically Disordered Protein by Protein Engineering
| Autor: | Maurizio Brunori, Stefano Gianni, Francesca Troilo, Daniela Bonetti, Sonia Longhi, Angelo Toto |
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| Přispěvatelé: | Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Protein Folding [SDV.BIO]Life Sciences [q-bio]/Biotechnology MESH: Protein Folding [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Intrinsically disordered proteins single-amino acid substitutions folding Cooperativity Protein Engineering 010402 general chemistry 01 natural sciences Biochemistry [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity Viral Proteins 03 medical and health sciences Protein Domains [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Measles Virus Nucleoprotein MESH: Intrinsically Disordered Proteins [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Chemistry Protein engineering Nucleocapsid Proteins MESH: Viral Proteins [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology 0104 chemical sciences [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] Intrinsically Disordered Proteins Folding (chemistry) MESH: Protein Engineering [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] Nucleoproteins 030104 developmental biology Measles virus Phosphoprotein [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Biophysics MESH: Nucleoproteins [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology MESH: Protein Domains MESH: Measles virus |
| Zdroj: | Biochemistry Biochemistry, American Chemical Society, 2017, 56 (29), pp.3780-3786. ⟨10.1021/acs.biochem.7b00350⟩ Biochemistry, 2017, 56 (29), pp.3780-3786. ⟨10.1021/acs.biochem.7b00350⟩ |
| ISSN: | 0006-2960 1520-4995 |
| DOI: | 10.1021/acs.biochem.7b00350⟩ |
| Popis: | International audience; Intrinsically disordered proteins (IDPs) are functionally active despite lacking a well-defined three-dimensional structure. Such proteins often undergo a disorder-to-order transition, or induced folding, when binding to their specific physiological partner. Because of cooperativity, the folding and binding steps typically appear as a single event, and therefore, induced folding is extremely difficult to characterize experimentally. In this perspective, the interaction between the disordered C-terminal domain of the measles virus nucleoprotein NTAIL and the folded X domain of the viral phosphoprotein (XD) is particularly interesting because the inherent complexity of the observed kinetics allows characterization of the binding and folding steps individually. Here we present a detailed structural description of the folding and binding events occurring in the recognition between NTAIL and XD. This result was achieved by measuring the effect of single-amino acid substitutions in NTAIL on the reaction mechanism. Analysis of the experimental data allowed us (i) to identify the key residues involved in the initial recognition between the two molecules and (ii) to depict the general features of the folding pathway of NTAIL. Furthermore, an analysis of the changes in stability obtained for the whole set of variants highlights how the sequence of this IDP has not been selected during evolution to fold efficiently. This feature might be a consequence of the weakly funneled nature of the energy landscape of IDPs in their unbound state and represents a plausible explanation of their highly dynamic nature even in the bound state, typically defined as "fuzziness". |
| Databáze: | OpenAIRE |
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