Effect of an amyloidogenic SARS-COV-2 protein fragment on α-synuclein monomers and fibrils

  1. Asis K. Jana
  2. Chance W. Lander
  3. Andrew D. Chesney
  4. Ulrich H. E. Hansmann

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Abstract

Using molecular dynamic simulations we study whether amyloidogenic regions in viral proteins can initiate and modulate formation of α-synuclein aggregates, thought to be the disease-causing agent in Parkinson’s Disease. 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 little effect of the stability of pre-existing or newly-formed fibrils.

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    SciScore for 10.1101/2022.02.21.481360: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Using the AutoDock Vina software20, we have generated start configurations for our simulations by docking SK9 segments in a ratio of 1:1 with the α-synuclein chains in the monomer and fibril systems described above.
    AutoDock Vina
    suggested: (AutoDock Vina, RRID:SCR_011958)
    The radius of gyration is calculated using the gmx_gyrate utility, while the residue-wise secondary structural propensity is computed with the Dictionary of Secondary Structure in Proteins (DSSP) as implemented in the GROMACS do_dssp tool.
    GROMACS
    suggested: (GROMACS, RRID:SCR_014565)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 5. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2022.02.21.481360v1 on bioRxiv