Dissecting Henipavirus W proteins conformational and fibrillation properties: contribution of their N‐ and C‐terminal constituent domains - Archive ouverte HAL
Journal Articles FEBS Journal Year : 2024

Dissecting Henipavirus W proteins conformational and fibrillation properties: contribution of their N‐ and C‐terminal constituent domains

Abstract

The Nipah and Hendra viruses are severe human pathogens. In addition to the P protein, their P gene also encodes the V and W proteins that share with P their N‐terminal intrinsically disordered domain (NTD) and possess distinct C‐terminal domains (CTDs). The W protein is a key player in the evasion of the host innate immune response. We previously showed that the W proteins are intrinsically disordered and can form amyloid‐like fibrils. However, structural information on W CTD (CTD W ) and its potential contribution to the fibrillation process is lacking. In this study, we demonstrate that CTD WS are disordered and able to form dimers mediated by disulfide bridges. We also show that the NTD and the CTD W interact with each other and that this interaction triggers both a gain of secondary structure and a chain compaction within the NTD. Finally, despite the lack of intrinsic fibrillogenic properties, we show that the CTD W favors the formation of fibrils by the NTD both in cis and in trans . Altogether, the results herein presented shed light on the molecular mechanisms underlying Henipavirus pathogenesis and may thus contribute to the development of targeted therapies.
Fichier principal
Vignette du fichier
Pesce et al FEBS J 2024.pdf (6.51 Mo) Télécharger le fichier
Origin Publication funded by an institution
Licence

Dates and versions

hal-04683726 , version 1 (02-09-2024)

Licence

Identifiers

Cite

Giulia Pesce, Frank Gondelaud, Denis Ptchelkine, Christophe Bignon, Patrick Fourquet, et al.. Dissecting Henipavirus W proteins conformational and fibrillation properties: contribution of their N‐ and C‐terminal constituent domains. FEBS Journal, 2024, Online ahead of print. ⟨10.1111/febs.17239⟩. ⟨hal-04683726⟩
18 View
5 Download

Altmetric

Share

More