title: Intrinsic disorder in measles virus nucleocapsids.
abstract: The genome of measles virus is encapsidated by multiple copies of the nucleoprotein (N), forming helical nucleocapsids of molecular mass approaching 150 Megadalton. The intrinsically disordered C-terminal domain of N (N(TAIL)) is essential for transcription and replication of the virus via interaction with the phosphoprotein P of the viral polymerase complex. The molecular recognition element (MoRE) of N(TAIL) that binds P is situated 90 amino acids from the folded RNA-binding domain (N(CORE)) of N, raising questions about the functional role of this disordered chain. Here we report the first in situ structural characterization of N(TAIL) in the context of the entire N-RNA capsid. Using nuclear magnetic resonance spectroscopy, small angle scattering, and electron microscopy, we demonstrate that N(TAIL) is highly flexible in intact nucleocapsids and that the MoRE is in transient interaction with N(CORE). We present a model in which the first 50 disordered amino acids of N(TAIL) are conformationally restricted as the chain escapes to the outside of the nucleocapsid via the interstitial space between successive N(CORE) helical turns. The model provides a structural framework for understanding the role of N(TAIL) in the initiation of viral transcription and replication, placing the flexible MoRE close to the viral RNA and, thus, positioning the polymerase complex in its functional environment.
authors: Institut de Biologie Structurale Jean-Pierre Ebel, Commissariat à l'Energie Atomique, Centre National de la Recherche Scientifique, Université Joseph Fourier, 41 Rue Jules Horowitz, 38027 Grenoble, France.
authors: Malene Ringkjøbing
authors: MR
authors: Jensen
authors: Guillaume
authors: G
authors: Communie
authors: Euripedes Almeida
authors: EA
authors: Ribeiro
authors: Nicolas
authors: N
authors: Martinez
authors: Ambroise
authors: A
authors: Desfosses
authors: Loïc
authors: L
authors: Salmon
authors: Luca
authors: L
authors: Mollica
authors: Frank
authors: F
authors: Gabel
authors: Marc
authors: M
authors: Jamin
authors: Sonia
authors: S
authors: Longhi
authors: Rob W H
authors: RW
authors: Ruigrok
authors: Martin
authors: M
authors: Blackledge
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