title: The intrinsically disordered C-terminal domain of the measles virus nucleoprotein interacts with the C-terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded.
abstract: Measles virus is a negative-sense, single-stranded RNA virus within the Mononegavirales order,which includes several human pathogens, including rabies, Ebola, Nipah, and Hendra viruses. The measles virus nucleoprotein consists of a structured N-terminal domain, and of an intrinsically disordered C-terminal domain, N(TAIL) (aa 401-525), which undergoes induced folding in the presence of the C-terminal domain (XD, aa 459-507) of the viral phosphoprotein. With in N(TAIL), an alpha-helical molecular recognition element (alpha-MoRE, aa 488-499) involved in binding to P and in induced folding was identified and then observed in the crystal structure of XD. Using small-angle X-ray scattering, we have derived a low-resolution structural model of the complex between XD and N(TAIL), which shows that most of N(TAIL) remains disordered in the complex despite P-induced folding within the alpha-MoRE. The model consists of an extended shape accommodating the multiple conformations adopted by the disordered N-terminal region of N(TAIL), and of a bulky globular region, corresponding to XD and to the C terminus of N(TAIL) (aa 486-525). Using surface plasmon resonance, circular dichroism, fluorescence spectroscopy, and heteronuclear magnetic resonance, we show that N(TAIL) has an additional site (aa 517-525) involved in binding to XD but not in the unstructured-to-structured transition. This work provides evidence that intrinsically disordered domains can establish complex interactions with their partners, and can contact them through multiple sites that do not all necessarily gain regular secondary structure.
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 6098 CNRS at Universités Aix-Marseille I et II, ESIL, Campus de Luminy, 13288 Marseille Cedex 09, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bourhis
authors.forename: Véronique
authors.initials: V
authors.lastname: Receveur-Bréchot
authors.forename: Michael
authors.initials: M
authors.lastname: Oglesbee
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Zhang
authors.forename: Matthew
authors.initials: M
authors.lastname: Buccellato
authors.forename: Hervé
authors.initials: H
authors.lastname: Darbon
authors.forename: Bruno
authors.initials: B
authors.lastname: Canard
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Finet
authors.forename: Sonia
authors.initials: S
authors.lastname: Longhi
mesh_terms: D001665:Binding Sites; D003001:Cloning, Molecular; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D017384:Sequence Deletion; D013050:Spectrometry, Fluorescence; D020349:Surface Plasmon Resonance; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014965:X-Rays
chemical_list: D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; C055859:P protein, Sendai virus; D010750:Phosphoproteins; D014764:Viral Proteins; C058314:nucleoprotein, Measles virus