FC0063
Measles virus nucleoprotein (N)  -  Measles virus nucleocapsid

Biological function
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.

Domain organization/sequence features
N consists of two domains: N_CORE (residues 1–400), responsible for the interaction with the viral RNA and for maintaining the nucleocapsid structure, and a long intrinsically disordered domain, N_TAIL (residues 401–525) serving as the anchor point for the polymerase complex. The molecular recognition element (MoRE) (residues 485–502) of the disordered N_TAIL interacts with the C-terminal three-helix bundle domain, XD, of P (residues 459–507) and thereby recruits the polymerase complex onto the nucleocapsid template.

Structural evidence
The molecular recognition element (MoRE, 485-502) of NTAIL that binds P is situated 90 amino acids from the folded RNA- binding domain (N_CORE) of N. 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, it was demonstrated that N_TAIL is highly flexible in intact nucleocapsids and that the MoRE is in transient interaction with N_CORE. Although the MoRE folds upon binding, the remainder of the 90 amino acid long N-terminal chain between the interaction site and N_CORE remains flexible. Signals for the first 50 amino acids (residues 401–450) are absent, while large variations of peak intensities indicate differential flexibility along the remainder of the chain. Hence, the first 50 amino acids of N_TAIL retain conformational disorder in the complex.

Structure/Mechanism
The first 50 disordered amino acids form an articulated spacer that allows the MoRE to escape from the interior of the capsid via the confined interstitial space between successive turns of the helix. The remainder of the chain, on the other hand, is more mobile, and retains the conformational sampling that exists in the isolated form of the protein. This sampling includes the conformational equilibrium of rapidly interconverting helical elements in the MoRE that is predefined by the primary sequence. The C-terminal region has been found to interact with the major inducible heat shock protein hsp70, which modulates both viral transcription and replication.

Mechanism category
Tethering

Significance
Fuzziness of N_TAIL facilitates transient interactions between the MoRE and the capsid surface, which provides spatial constraints for polymerase interactions and also facilitates the access of the polymerase without major rearrangements of the nucleocapsid.

Submitted by
Martin Blackledge   martin.blackledge@ibs.fr