title: Solution structure of the C-terminal X domain of the measles virus phosphoprotein and interaction with the intrinsically disordered C-terminal domain of the nucleoprotein.
abstract: In this report, the solution structure of the nucleocapsid-binding domain of the measles virus phosphoprotein (XD, aa 459-507) is described. A dynamic description of the interaction between XD and the disordered C-terminal domain of the nucleocapsid protein, (N(TAIL), aa 401-525), is also presented. XD is an all alpha protein consisting of a three-helix bundle with an up-down-up arrangement of the helices. The solution structure of XD is very similar to the crystal structures of both the free and bound form of XD. One exception is the presence of a highly dynamic loop encompassing XD residues 489-491, which is involved in the embedding of the alpha-helical XD-binding region of N(TAIL). Secondary chemical shift values for full-length N(TAIL) were used to define the precise boundaries of a transient helical segment that coincides with the XD-binding domain, thus shedding light on the pre-recognition state of N(TAIL). Titration experiments with unlabeled XD showed that the transient alpha-helical conformation of N(TAIL) is stabilized upon binding. Lineshape analysis of NMR resonances revealed that residues 483-506 of N(TAIL) are in intermediate exchange with XD, while the 475-482 and 507-525 regions are in fast exchange. The N(TAIL) resonance behavior in the titration experiments is consistent with a complex binding model with more than two states.
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 6098, CNRS, France and Universités d'Aix-Marseille I and II, 163 Avenue de Luminy, 13288 Marseille Cedex 09, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gely
authors.forename: David F
authors.initials: DF
authors.lastname: Lowry
authors.forename: Cédric
authors.initials: C
authors.lastname: Bernard
authors.forename: Malene R
authors.initials: MR
authors.lastname: Jensen
authors.forename: Martin
authors.initials: M
authors.lastname: Blackledge
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Costanzo
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bourhis
authors.forename: Hervé
authors.initials: H
authors.lastname: Darbon
authors.forename: Gary
authors.initials: G
authors.lastname: Daughdrill
authors.forename: Sonia
authors.initials: S
authors.lastname: Longhi
mesh_terms: D018360:Crystallography, X-Ray; D008459:Measles virus / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000737:chemistry* / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012996:Solutions
chemical_list: D009698:Nucleoproteins; D010750:Phosphoproteins; D012996:Solutions