Paramyxoviruses cause measles and mumps, the once familiar diseases of early childhood. Other members of this family, such as the bat-borne Menangle virus, present an emerging threat to human health. These viruses possess a unique machinery for replicating and transcribing their genomic RNA, which provides an attractive drug target.
The replicative complex of paramyxoviruses is comprised of three proteins. The nucleocapsid protein (N) packages and organizes the genomic RNA, while the phosphoprotein (P) and the large (L) protein together form the viral RNA-dependent RNA polymerase (RdRp), which replicates and transcribes the genome. L encompasses all enzymatic activities of the RdRp,1 while P assists the RdRp to engage and move along its protein-RNA template.2 The ability to act on packaged RNA is the defining feature of the paramyxoviral RdRp, which is without cellular parallel.
P is a functionally active tetramer, which is oligomerized through a centrally located coiled-coil. The region that mediates attachment of the RdRp to its template is C-terminal to the coiled coil. This ~120 amino acid sequence consists of a structured template-binding domain, which is tethered to the coiled coil by an intrinsically disordered linker. The high degree of flexibility in the linker region is believed to be critical for polymerase movement.3
Testing this hypothesis requires the detailed investigation of the structure and dynamics of the P protein, which can be achieved using nuclear magnetic resonance (NMR) spectroscopy. Here we present near complete NMR chemical shift assignments for the C-terminal region of the Menangle virus P protein, and report on the dynamic behaviour of this highly flexible protein.