Article Dans Une Revue International Journal of Molecular Sciences Année : 2023

Molecular Determinants of Fibrillation in a Viral Amyloidogenic Domain from Combined Biochemical and Biophysical Studies

Résumé

The Nipah and Hendra viruses (NiV and HeV) are biosafety level 4 human pathogens classified within the Henipavirus genus of the Paramyxoviridae family. In both NiV and HeV, the gene encoding the Phosphoprotein (P protein), an essential polymerase cofactor, also encodes the V and W proteins. These three proteins, which share an intrinsically disordered N-terminal domain (NTD) and have unique C-terminal domains (CTD), are all known to counteract the host innate immune response, with V and W acting by either counteracting or inhibiting Interferon (IFN) signaling. Recently, the ability of a short region within the shared NTD (i.e., PNT3) to form amyloid-like structures was reported. Here, we evaluated the relevance of each of three contiguous tyrosine residues located in a previously identified amyloidogenic motif (EYYY) within HeV PNT3 to the fibrillation process. Our results indicate that removal of a single tyrosine in this motif significantly decreases the ability to form fibrils independently of position, mainly affecting the elongation phase. In addition, we show that the C-terminal half of PNT3 has an inhibitory effect on fibril formation that may act as a molecular shield and could thus be a key domain in the regulation of PNT3 fibrillation. Finally, the kinetics of fibril formation for the two PNT3 variants with the highest and the lowest fibrillation propensity were studied by Taylor Dispersion Analysis (TDA). The results herein presented shed light onto the molecular mechanisms involved in fibril formation.

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relationship_isVariantFormatOf hal-04245075 Preprint Juliet F Nilsson, Hakima Baroudi, Frank Gondelaud, Giulia Pesce, Christophe Bignon, et al.. Molecular determinants of fibrillation in a viral amyloidogenic domain from combined biochemical and biophysical studies. 2022. ⟨hal-04245075⟩

hal-04245075 est un preprint déposé dans bioRxiv
Recherche Data Gouv

Cite 10.57745/S3MIGF Jeu de données LONGHI, Sonia, 2025, "Nilsson et al Determinants of Fibrillation in a Viral Amyloidogenic Domain from Combined Biochemical and Biophysical Studies. Int J Mol Sci. 2022 24(1):399. doi: 10.3390/ijms24010399", https://doi.org/10.57745/S3MIGF, Recherche Data Gouv, V1

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hal-03952101 , version 1 (23-01-2023)

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Juliet F Nilsson, Hakima Baroudi, Frank Gondelaud, Giulia Pesce, Christophe Bignon, et al.. Molecular Determinants of Fibrillation in a Viral Amyloidogenic Domain from Combined Biochemical and Biophysical Studies. International Journal of Molecular Sciences, 2023, 24 (1), pp.399. ⟨10.3390/ijms24010399⟩. ⟨hal-03952101⟩
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