Demonstration of a Folding after Binding Mechanism in the Recognition between the Measles Virus N-TAIL and X Domains
| Autor: | Daniela Bonetti, Angela Morrone, Eva Di Silvio, Stefano Gianni, Marion Dosnon, Jenny Erales, Sonia Longhi |
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| Přispěvatelé: | 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: | 2015 |
| Předmět: |
Models
Molecular folding Protein Folding Gene Expression Computational biology Biochemistry Protein Structure Secondary Measles virus Viral Proteins 03 medical and health sciences Escherichia coli Protein Interaction Domains and Motifs disorder-to order transition ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences intrinsically disordered proteins (IDPs) biology [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Mechanism (biology) Chemistry 030302 biochemistry & molecular biology viral phosphoprotein General Medicine Nucleocapsid Proteins Phosphoproteins biology.organism_classification Virology [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] Intrinsically Disordered Proteins Folding (chemistry) Kinetics [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] Nucleoproteins Thermodynamics Molecular Medicine Protein Binding |
| Zdroj: | ACS Chemical Biology ACS Chemical Biology, American Chemical Society, 2015, 10 (3), pp.795-802. ⟨10.1021/cb5008579⟩ ACS Chemical Biology, 2015, 10 (3), pp.795-802. ⟨10.1021/cb5008579⟩ |
| ISSN: | 1554-8929 1554-8937 |
| Popis: | In the past decade, a wealth of experimental data has demonstrated that a large fraction of proteins, while functional, are intrinsically disordered at physiological conditions. Many intrinsically disordered proteins (IDPs) undergo a disorder-to-order transition upon binding to their biological targets, a phenomenon known as induced folding. Induced folding may occur through two extreme mechanisms, namely conformational selection and folding after binding. Although the pre-existence of ordered structures in IDPs is a prerequisite for conformational selection, it does not necessarily commit to this latter mechanism, and kinetic studies are needed to discriminate between the two possible scenarios. So far, relatively few studies have addressed this issue from an experimental perspective. Here, we analyze the interaction kinetics between the intrinsically disordered C-terminal domain of the measles virus nucleoprotein (NTAIL) and the X domain (XD) of the viral phosphoprotein. Data reveal that NTAIL recognizes XD by first forming a weak encounter complex in a disordered conformation, which is subsequently locked-in by a folding step; i.e., binding precedes folding. The implications of our kinetic results, in the context of previously reported equilibrium data, are discussed. These results contribute to enhancing our understanding of the molecular mechanisms by which IDPs recognize their partners and represent a paradigmatic example of the need of kinetic methods to discriminate between reaction mechanisms. |
| Databáze: | OpenAIRE |
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