FC0015
Measles virus nucleoprotein  -  Phosphoprotein

Biological function
The nucleoprotein (N)-phosphoprotein (XD) interaction is required for replication of Measles virus.

Structural evidence
Upon binding of nucleoprotein N_TAIL to XD only 18 residues out of 125 (401-525) adopt a well-defined α-helical structure and serve as an alpha-MoRE. SAXS indicates an extended ensemble for 401-487 region and multiple, yet compact conformation for 506-525 region, which packs against the XD binding site. The absence of the 517-525 region significantly reduces the helical propensity of the Box2 (α-MoRE) region. Distinct conformers were also detected by electrospray ionization-mass spectrometry (ESI-MS) and ion mobility.

Biochemical evidence
Hydrophobic residues in fuzzy regions of Measles virus N_TAIL establish transient interactions with the target and contribute to binding affinity. Region 517-525 decreases K_D from 8.1 x 10^-8M to 1.2 x 10^{- 5} M.

Structure/Mechanism
N is anchored to P via an α-helical element, which is located within the disordered N_TAIL. In the context of the full Measles virus nucleocapsid, regions connecting the molecular recognition element (MoRE) of N_TAIL to the globular domain (90 AA) remain also largely dynamic. The disordered character of N_TAIL facilitates transient interactions between the MoRE and the capsid surface, which provides spatial constraints for polymerase interactions.

Mechanism category
conformational selection

Significance
Fuzziness of N facilitates the access of the polymerase without major rearrangements of the nucleocapsid.

Submitted by
Sonia Longhi   sonia.longhi@afmb.univ-mrs.fr