Structural Superimposition

Abstact

Nipah virus (NiV) is a BSL-4 zoonotic paramyxovirus with ~75% human mortality. The matrix protein (M) of NiV and other paramyxoviruses binds the inner leaflet of the cellular plasma membrane, orchestrating virion assembly by bringing together transmembrane glycoproteins (F/G) and ribonucleoprotein complexes (N). However, the interactions of these full-length proteins within membrane complexes remain elusive. Using cryo-electron tomography and subtomogram averaging of virus like particles (VLPs), we interrogated the protein:protein interactions of the main NiV structural proteins M/N/F/G. The M lattice structure determined to 7A revealed a novel M-dimer arrangement that yielded two distinct repeating holes. Notably, F-trimers were arranged above only one of the two holes, dependent on F's cytoplasmic tail. G was enriched in regions of higher M-VLP curvature, while N dramatically increased M-VLP pleomorphism. This work provides novel insights into paramyxoviral protein complexes, structures, and morphology.