title: The C-terminal domain of the measles virus nucleoprotein is intrinsically disordered and folds upon binding to the C-terminal moiety of the phosphoprotein.
abstract: The nucleoprotein of measles virus consists of an N-terminal moiety, N(CORE), resistant to proteolysis and a C-terminal moiety, N(TAIL), hypersensitive to proteolysis and not visible as a distinct domain by electron microscopy. We report the bacterial expression, purification, and characterization of measles virus N(TAIL). Using nuclear magnetic resonance, circular dichroism, gel filtration, dynamic light scattering, and small angle x-ray scattering, we show that N(TAIL) is not structured in solution. Its sequence and spectroscopic and hydrodynamic properties indicate that N(TAIL) belongs to the premolten globule subfamily within the class of intrinsically disordered proteins. The same epitopes are exposed in N(TAIL) and within the nucleoprotein, which rules out dramatic conformational changes in the isolated N(TAIL) domain compared with the full-length nucleoprotein. Most unstructured proteins undergo some degree of folding upon binding to their partners, a process termed "induced folding." We show that N(TAIL) is able to bind its physiological partner, the phosphoprotein, and that it undergoes such an unstructured-to-structured transition upon binding to the C-terminal moiety of the phosphoprotein. The presence of flexible regions at the surface of the viral nucleocapsid would enable plastic interactions with several partners, whereas the gain of structure arising from induced folding would lead to modulation of these interactions. These results contribute to the study of the emerging field of natively unfolded proteins.
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, UMR 6098 CNRS et Université Aix-Marseille I et II, ESIL, Campus de Luminy, 13288 Marseille Cedex 09, France. longhi@afmb.cnrs-mrs.fr
authors.forename: Sonia
authors.initials: S
authors.lastname: Longhi
authors.forename: Véronique
authors.initials: V
authors.lastname: Receveur-Bréchot
authors.forename: David
authors.initials: D
authors.lastname: Karlin
authors.forename: Kenth
authors.initials: K
authors.lastname: Johansson
authors.forename: Hervé
authors.initials: H
authors.lastname: Darbon
authors.forename: David
authors.initials: D
authors.lastname: Bhella
authors.forename: Robert
authors.initials: R
authors.lastname: Yeo
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Finet
authors.forename: Bruno
authors.initials: B
authors.lastname: Canard
mesh_terms: D002850:Chromatography, Gel; D002942:Circular Dichroism; D000939:Epitopes; D004926:Escherichia coli / Q000378:metabolism; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism; D014965:X-Rays
chemical_list: D000939:Epitopes; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D014764:Viral Proteins; C058314:nucleoprotein, Measles virus