Structure Model Analysis Of Phosphorylation Dependent Binding And Sequestration Of SARS-COV-2 Encoded Nucleocapsid Protein By Protein 14-3-3

  1. Pierre Limtung
  2. H.Y. Lim Tung

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Abstract

Phosphorylation of serines 197 and 206 of SARS-COV-2 Nucleocapsid protein (NCp) enhanced the stability and binding efficiency and sequestration of NCp to Protein 14-3-3 by increasing the Stability Energy (ΔGstability energy) and Binding Energy (ΔΔGbinding energy) from ~545 Kcal/mol to ~616 Kcal/mol, and from 108 Kcal/mol to ~228 Kcal/mol respectively. The calculated Binding Energy Difference (ΔΔGbinding energy difference) between dephospho-NCp-14-3-3 complex and phospho-NCp-13-3-3 complex was ~72 Kcal/mol. Phosphorylations of serines 186, 197, 202 and 206, and threonines 198 and 205 NCp also caused an increase in the Stability Energy (ΔGstability energy) and Binding Energy (ΔΔGbinding energy) from ~545 Kcal/mol to ~617, 616, 583, 580, 574, 564 and 566 Kcal/mol and from ~108 Kcal/mol to ~228, 216, 184, 188, 184, 174 and 112 Kcal/mol respectively. Phosphorylation of NCp on serines 197 and 206 caused a decrease in Stability Energy and Binding Energy from ~698 Kcal/mol to 688 Kcal/mol, and from ~91 Kcal/mol to ~82 Kcal/mol for the dimerization of NCp. These results support the existence of a phosphorylation dependent cellular mechanism to bind and sequester NCp.

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    SciScore for 10.1101/2020.09.16.299362: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    NCps rendered in this work and Protein 14-3-3 (1YZ5) based on the structure determination of Benzinger et al. [40] were analyzed and visualized by the CCP4 Molecular Graphics Program Version 2.10.11 as described by Mc Nicolas et al [41] and the ZMM Molecular Modeling Program as described by Garden and Zhorov [42].
    CCP4 Molecular Graphics Program
    suggested: (CCP4mg, RRID:SCR_019041)
    Molecular
    suggested: (SAXS Molecular Weight, RRID:SCR_018137)
    Binding Energy (ΔΔGbinding energy) of protein complex was determined and calculated using the Analyze Complex Program of FoldX as described by Guerois et al. and Schymkowitz et al. [37, 38].
    FoldX
    suggested: (FoldX, RRID:SCR_008522)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    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: We did not find any issues relating to colormaps.

    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.

    About SciScore

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  2. Version published to 10.1101/2020.09.16.299362v1 on bioRxiv