Biochemical and structural studies of the oligomerization domain of the Nipah virus phosphoprotein: Evidence for an elongated coiled-coil homotrimer

- Paramyxoviral phosphoproteins are known to oligomerize through coiled-coils.
- All paramyxoviral phosphoproteins studied so far are tetramers.
- We purified and characterized the Nipah virus P protein multimerization domain (PMD).
- We show that PMD forms a very stable and elongated coiled-coil trimer.
- This is the first report of a Paramyxoviridae P protein forming trimers.

Nipah virus (NiV) is a recently emerged severe human pathogen that belongs to the Henipavirus genus within the Paramyxoviridae family. The NiV genome is encapsidated by the nucleoprotein (N) within a helical nucleocapsid that is the substrate used by the polymerase for transcription and replication. The polymerase is recruited onto the nucleocapsid via its cofactor, the phosphoprotein (P). The NiV P protein has a modular organization, with alternating disordered and ordered domains. Among these latter, is the P multimerization domain (PMD) that was predicted to adopt a coiled-coil conformation. Using both biochemical and biophysical approaches, we show that NiV PMD forms a highly stable and elongated coiled-coil trimer, a finding in striking contrast with respect to the PMDs of Paramyxoviridae members investigated so far that were all found to tetramerize. The present results therefore represent the first report of a paramyxoviral P protein forming trimers.