Structural highlights
Function
PHOSP_NIPAV Essential component of the RNA polymerase transcription and replication complex. Binds the viral ribonucleocapsid and positions the L polymerase on the template (By similarity). May play a role to prevent the establishment of cellular antiviral state by binding to host STAT1 in the cytoplasm. This activity is not as strong as that of V and W.
Publication Abstract from PubMed
To understand the dynamic interactions between the phosphoprotein (P) and the nucleoprotein (N) within the transcription/replication complex of the Paramyxoviridae and to decipher their roles in regulating viral multiplication, we characterized the structural properties of the C-terminal X domain (PXD) of Nipah (NiV) and Hendra virus (HeV) P protein. In crystals, isolated NiV PXD adopted a two-helix dimeric conformation, which was incompetent for binding its partners, but in complex with the C-terminal intrinsically disordered tail of the N protein (NTAIL), it folded into a canonical 3H bundle conformation. In solution, SEC-MALLS, SAXS and NMR spectroscopy experiments indicated that both NiV and HeV PXD were larger in size than expected for compact proteins of the same molecular mass and were in conformational exchange between a compact three-helix (3H) bundle and partially unfolded conformations, where helix alpha3 is detached from the other two. Some measurements also provided strong evidence for dimerization of NiV PXD in solution but not for HeV PXD. Ensemble modeling of experimental SAXS data and statistical-dynamical modeling reconciled all these data, yielding a model where NiV and HeV PXD exchanged between different conformations, and where NiV but not HeV PXD formed dimers. Finally, recombinant NiV comprising a chimeric P carrying HeV PXD was rescued and compared with parental NiV. Experiments carried out in cellula demonstrated that the replacement of PXD did not significantly affect the replication dynamics while caused a slight virus attenuation, suggesting a possible role of the dimerization of NiV PXD in viral replication.
Structural Dynamics of the C-terminal X Domain of Nipah and Hendra Viruses Controls the Attachment to the C-terminal Tail of the Nucleocapsid Protein.,Bourhis JM, Yabukarski F, Communie G, Schneider R, Volchkova VA, Freneat M, Gerard FC, Ducournau C, Mas C, Tarbouriech N, Ringkjobing Jensen M, Volchkov VE, Blackledge M, Jamin M J Mol Biol. 2022 Mar 19;434(10):167551. doi: 10.1016/j.jmb.2022.167551. PMID:35317998[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bourhis JM, Yabukarski F, Communie G, Schneider R, Volchkova VA, Freneat M, Gerard FC, Ducournau C, Mas C, Tarbouriech N, Ringkjobing Jensen M, Volchkov VE, Blackledge M, Jamin M. Structural Dynamics of the C-terminal X Domain of Nipah and Hendra Viruses Controls the Attachment to the C-terminal Tail of the Nucleocapsid Protein. J Mol Biol. 2022 Mar 19;434(10):167551. doi: 10.1016/j.jmb.2022.167551. PMID:35317998 doi:http://dx.doi.org/10.1016/j.jmb.2022.167551
