Among the viruses with the greatest pandemic potential are the paramyxoviruses. This family of RNA viruses infects most, if not all, vertebrate species and includes established human pathogens such as measles, mumps and parainfluenza viruses 1-4, as well as highly virulent emerging zoonotic pathogens like Hendra and Nipah virus.
The RNA genome of paramyxoviruses is bound and encapsidated by the viral nucleoprotein, creating a helical protein-RNA complex termed the nucleocapsid. The nucleocapsid protects and organises the genome, obligatorily acting as the template for both transcription and genome replication. As the nucleoprotein binds RNA avidly and non-specifically, a mechanism is required to block binding of cellular RNA and maintain the nucleoprotein in a monomeric state, suitable for loading onto the nascent viral genome during genome replication. This “chaperone” function is provided by the multifunctional and structurally-diverse viral phosphoprotein, via a conserved linear sequence motif – the Soyuz-1 motif – which is located within the intrinsically disordered N-terminal region of the phosphoprotein.
In several paramyxoviruses, the Soyuz-1 motif has been shown to bind to the viral nucleoprotein in an α-helical configuration thereby blocking oligomerisation and RNA binding. But questions remain about the generality of this mechanism, and the extent to which binding and folding of the Soyuz-1 motif are coupled. To help address these questions, I will detail progress in characterising the Soyuz motifs from Menangle virus - a bat-borne paramyxovirus - both in isolation and in complex with the viral nucleoprotein. Characterisation of the isolated Soyuz motifs rests heavily on spectroscopic techniques, including circular dichroism and nuclear magnetic resonance spectroscopy, while the structure of the complex is being determined using X-ray crystallography.