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

Pesce, Giulia; Gondelaud, Frank; Ptchelkine, Denis; Nilsson, Juliet F.; Bignon, Christophe; Cartalas, Jérémy; Fourquet, Patrick; Longhi, Sonia

doi:10.3390/ijms23020923

Open AccessArticle

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

by

Giulia Pesce

^1,†,

Frank Gondelaud

^1,†,

Denis Ptchelkine

¹,

Juliet F. Nilsson

¹

,

Christophe Bignon

¹,

Jérémy Cartalas

¹,

Patrick Fourquet

²

and

Sonia Longhi

^1,*

¹

Laboratoire Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257, Aix Marseille University and Centre National de la Recherche Scientifique (CNRS), 163 Avenue de Luminy, Case 932, 13288 Marseille, France

²

INSERM, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS), Marseille Protéomique, Institut Paoli-Calmettes, Aix Marseille University, 27 Bvd Leï Roure, CS 30059, 13273 Marseille, France

^*

Author to whom correspondence should be addressed.

^†

Equal contribution to the work.

Int. J. Mol. Sci. 2022, 23(2), 923; https://doi.org/10.3390/ijms23020923

Submission received: 15 December 2021 / Revised: 10 January 2022 / Accepted: 12 January 2022 / Published: 15 January 2022

(This article belongs to the Special Issue Intrinsically Disordered Proteins (IDPs): From Physical Chemistry to Pathogenic Mechanisms)

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Abstract

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.

Keywords: intrinsically disordered proteins/regions; small-angle X-ray scattering; innate immune response evasion; phase separation; fibrillation; biocondensates; Congo red and Thioflavin T binding assays; negative-staining electron microscopy; amyloid-like fibrils; viral proteins

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MDPI and ACS Style

Pesce, G.; Gondelaud, F.; Ptchelkine, D.; Nilsson, J.F.; Bignon, C.; Cartalas, J.; Fourquet, P.; Longhi, S. Experimental Evidence of Intrinsic Disorder and Amyloid Formation by the Henipavirus W Proteins. Int. J. Mol. Sci. 2022, 23, 923. https://doi.org/10.3390/ijms23020923

AMA Style

Pesce G, Gondelaud F, Ptchelkine D, Nilsson JF, Bignon C, Cartalas J, Fourquet P, Longhi S. Experimental Evidence of Intrinsic Disorder and Amyloid Formation by the Henipavirus W Proteins. International Journal of Molecular Sciences. 2022; 23(2):923. https://doi.org/10.3390/ijms23020923

Chicago/Turabian Style

Pesce, Giulia, Frank Gondelaud, Denis Ptchelkine, Juliet F. Nilsson, Christophe Bignon, Jérémy Cartalas, Patrick Fourquet, and Sonia Longhi. 2022. "Experimental Evidence of Intrinsic Disorder and Amyloid Formation by the Henipavirus W Proteins" International Journal of Molecular Sciences 23, no. 2: 923. https://doi.org/10.3390/ijms23020923

APA Style

Pesce, G., Gondelaud, F., Ptchelkine, D., Nilsson, J. F., Bignon, C., Cartalas, J., Fourquet, P., & Longhi, S. (2022). Experimental Evidence of Intrinsic Disorder and Amyloid Formation by the Henipavirus W Proteins. International Journal of Molecular Sciences, 23(2), 923. https://doi.org/10.3390/ijms23020923

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

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