biostudies-literatureGondelaud FAgence Nationale de la RechercheFondation pour la Recherche Médicalee70085https://www.ebi.ac.uk/biostudies/studies/S-EPMC11917119biostudies-literatureUnknown34(4)The Hendra (HeV) and Nipah (NiV) viruses are high-priority, biosafety level-4 pathogens that cause fatal neurological and respiratory disease. Their P gene encodes not only the P protein, an essential polymerase cofactor, but also the virulence factors V and W. We previously showed that the W protein of HeV (W^HeV) forms amyloid-like fibrils and that one of its subdomains, PNT3, fibrillates in isolation. However, the fibrillation kinetics is much faster in the case of the full-length W^HeV compared to PNT3, suggesting that another W^HeV region contributes to the fibrillation process. In this work, we identified the region spanning residues 2-110 (PNT1) as the crucial region implicated in W^HeV fibrillation. Through site-directed mutagenesis, combinedProtein science : a publication of the Protein SocietyA conserved motif in Henipavirus P/V/W proteins drives the fibrillation of the W protein from Hendra virus.PMC11917119ANR‐21‐CE11‐ 0012‐01MND202310017898ANR‐10‐INSB‐ 0005ANR-10-INSB- 0005ANR-21-CE11- 0012-01Gondelaud FBignon CCarriere FPtchelkine DLonghi SfalseA conserved motif in Henipavirus P/V/W proteins drives the fibrillation of the W protein from Hendra virus.The Hendra (HeV) and Nipah (NiV) viruses are high-priority, biosafety level-4 pathogens that cause fatal neurological and respiratory disease. Their P gene encodes not only the P protein, an essential polymerase cofactor, but also the virulence factors V and W. We previously showed that the W protein of HeV (W^HeV) forms amyloid-like fibrils and that one of its subdomains, PNT3, fibrillates in isolation. However, the fibrillation kinetics is much faster in the case of the full-length W^HeV compared to PNT3, suggesting that another W^HeV region contributes to the fibrillation process. In this work, we identified the region spanning residues 2-110 (PNT1) as the crucial region implicated in W^HeV fibrillation. Through site-directed mutagenesis, combined2025-01-01T00:00:00Z2025 Apr2026-06-02T07:19:29.531Z2025-04-21T16:53:32.688ZS-EPMC119171194010013310.1002/pro.70085