Effect of an Amyloidogenic SARS-COV‑2 Protein Fragment on α‑Synuclein Monomers and Fibrils

Aggregates of α-synuclein are thought to be the disease-causing agent in Parkinson’s disease. Various case studies have hinted at a correlation between COVID-19 and the onset of Parkinson’s disease. For this reason, we use molecular dynamics simulations to study whether amyloidogenic regions in SARS...

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Bibliographic Details
Published in:The journal of physical chemistry. B 2022-05, Vol.126 (20), p.3648-3658
Main Authors: Jana, Asis K., Lander, Chance W., Chesney, Andrew D., Hansmann, Ulrich H. E.
Format: Article
Language:English
Subjects:
alpha-Synuclein - chemistry
alpha-Synuclein - metabolism
Amyloidogenic Proteins - chemistry
Amyloidogenic Proteins - metabolism
B: Biophysical and Biochemical Systems and Processes
Coronavirus Envelope Proteins - chemistry
Coronavirus Envelope Proteins - metabolism
COVID-19 - virology
Humans
Parkinson Disease - metabolism
Peptide Fragments - chemistry
Peptide Fragments - metabolism
SARS-CoV-2 - metabolism
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Summary:Aggregates of α-synuclein are thought to be the disease-causing agent in Parkinson’s disease. Various case studies have hinted at a correlation between COVID-19 and the onset of Parkinson’s disease. For this reason, we use molecular dynamics simulations to study whether amyloidogenic regions in SARS-COV-2 proteins can initiate and modulate aggregation of α-synuclein. As an example, we choose the nine-residue fragment SFY­VYS­RVK (SK9), located on the C-terminal of the envelope protein of SARS-COV-2. We probe how the presence of SK9 affects the conformational ensemble of α-synuclein monomers and the stability of two resolved fibril polymorphs. We find that the viral protein fragment SK9 may alter α-synuclein amyloid formation by shifting the ensemble toward aggregation-prone and preferentially rod-like fibril seeding conformations. However, SK9 has only a small effect on the stability of pre-existing or newly formed fibrils. A potential mechanism and key residues for potential virus-induced amyloid formation are described.
ISSN:1520-6106
1520-5207
1520-5207
DOI:10.1021/acs.jpcb.2c01254