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Article Dans Une Revue International Journal of Molecular Sciences Année : 2022

Experimental Evidence of Intrinsic Disorder and Amyloid Formation by the Henipavirus W Proteins

Giulia Pesce
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Frank Gondelaud
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Denis Ptchelkine
Juliet F Nilsson
Christophe Bignon
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Jérémy Cartalas
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Résumé

Henipaviruses are severe human pathogens within the Paramyxoviridae family. Beyond the P protein, the Henipavirus P gene also encodes the V and W proteins which share with P their N-terminal, intrinsically disordered domain (NTD) and possess a unique C-terminal domain. Henipavirus W proteins antagonize interferon (IFN) signaling through NTD-mediated binding to STAT1 and STAT4, and prevent type I IFN expression and production of chemokines. Structural and molecular information on Henipavirus W proteins is lacking. By combining various bioinformatic approaches, we herein show that the Henipaviruses W proteins are predicted to be prevalently disordered and yet to contain short order-prone segments. Using limited proteolysis, differential scanning fluorimetry, analytical size exclusion chromatography, far-UV circular dichroism and small-angle X-ray scattering, we experimentally confirmed their overall disordered nature. In addition, using Congo red and Thioflavin T binding assays and negative-staining transmission electron microscopy, we show that the W proteins phase separate to form amyloid-like fibrils. The present study provides an additional example, among the few reported so far, of a viral protein forming amyloid-like fibrils, therefore significantly contributing to enlarge our currently limited knowledge of viral amyloids. In light of the critical role of the Henipavirus W proteins in evading the host innate immune response and of the functional role of phase separation in biology, these studies provide a conceptual asset to further investigate the functional impact of the phase separation abilities of the W proteins.
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Dates et versions

hal-03533043 , version 1 (18-01-2022)

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Giulia Pesce, Frank Gondelaud, Denis Ptchelkine, Juliet F Nilsson, Christophe Bignon, et al.. Experimental Evidence of Intrinsic Disorder and Amyloid Formation by the Henipavirus W Proteins. International Journal of Molecular Sciences, 2022, 23 (2), pp.923. ⟨10.3390/ijms23020923⟩. ⟨hal-03533043⟩
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