title: Structural Disorder within Paramyxoviral Nucleoproteins and Phosphoproteins in Their Free and Bound Forms: From Predictions to Experimental Assessment.
abstract: We herein review available computational and experimental data pointing to the abundance of structural disorder within the nucleoprotein (N) and phosphoprotein (P) from three paramyxoviruses, namely the measles (MeV), Nipah (NiV) and Hendra (HeV) viruses. We provide a detailed molecular description of the mechanisms governing the disorder-to-order transition that the intrinsically disordered C-terminal domain (NTAIL) of their N proteins undergoes upon binding to the C-terminal X domain (PXD) of the homologous P proteins. We also show that NTAIL-PXD complexes are "fuzzy", i.e., they possess a significant residual disorder, and discuss the possible functional significance of this fuzziness. Finally, we emphasize the relevance of N-P interactions involving intrinsically disordered proteins as promising targets for new antiviral approaches, and end up summarizing the general functional advantages of disorder for viruses.
authors.affiliation: Aix-Marseille Université, Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257, 163, Avenue de Luminy, Case 932, 13288 Marseille, France. jh884@cam.ac.uk.|Centre National pour la Recherche Scientifique (CNRS), AFMB UMR 7257, 163, Avenue de Luminy, Case 932, 13288 Marseille, France. jh884@cam.ac.uk.
authors.forename: Johnny
authors.initials: J
authors.lastname: Habchi
authors.affiliation: Aix-Marseille Université, Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257, 163, Avenue de Luminy, Case 932, 13288 Marseille, France. Sonia.Longhi@afmb.univ-mrs.fr.|Centre National pour la Recherche Scientifique (CNRS), AFMB UMR 7257, 163, Avenue de Luminy, Case 932, 13288 Marseille, France. Sonia.Longhi@afmb.univ-mrs.fr.
authors.forename: Sonia
authors.initials: S
authors.lastname: Longhi
mesh_terms: D004578:Electron Spin Resonance Spectroscopy; D016296:Mutagenesis; D019906:Nuclear Magnetic Resonance, Biomolecular; D009698:Nucleoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018098:Paramyxovirinae / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D009698:Nucleoproteins; D010750:Phosphoproteins; D014764:Viral Proteins
keywords: antiviral approaches; disorder prediction; fuzzy complexes; induced folding; intrinsic disorder; molecular recognition elements; nucleoprotein; paramyxoviruses; phosphoprotein; protein-protein interactions