Dynamics of the Intrinsically Disordered C-Terminal Domain of the Nipah Virus Nucleoprotein and Interaction with the X Domain of the Phosphoprotein as Unveiled by NMR Spectroscopy

We provide an atomic-resolution description based on NMR spectroscopy, of the intrinsically disordered C-terminal domain of the Nipah virus nucleoprotein (N-TAIL), both in its isolated state and within the nucleocapsid (NC). Within the NC the second half of N-TAIL retains conformational behavior similar to that of isolated N-TAIL, whereas the first half of N-TAIL becomes much more rigid. In spite of the mostly disordered nature of N-TAIL, chemical shifts and relaxation measurements show a significant degree of alpha-helical sampling in the molecular recogni-tion element (MoRE) involved in binding to the X domain (XD) of the phosphoprotein, with this preconfiguration being more pronounced than in the N-TAIL domain from the cognate Hendra virus. Outside the MoRE, an additional region exhibiting reduced flexibility was identified within N-TAIL and found to be involved in binding to the XD. H-1-and C-13-detected titration NMR experiments support a highly dynamic binding of N-TAIL at the surface of the XD.