Structure of SARS-CoV-2 ORF8, a rapidly evolving coronavirus protein implicated in immune evasion

  1. Thomas G. Flower
  2. Cosmo Z. Buffalo
  3. Richard M. Hooy
  4. Marc Allaire
  5. Xuefeng Ren
  6. James H. Hurley

Reviewed by

Read the full article

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

The molecular basis for the severity and rapid spread of the COVID-19 disease caused by SARS-CoV-2 is largely unknown. ORF8 is a rapidly evolving accessory protein that has been proposed to interfere with immune responses. The crystal structure of SARS-CoV-2 ORF8 was determined at 2.04 Å resolution by x-ray crystallography. The structure reveals a ~60 residue core similar to SARS-CoV ORF7a with the addition of two dimerization interfaces unique to SARS-CoV-2 ORF8. A covalent disulfide-linked dimer is formed through an N-terminal sequence specific to SARS-CoV-2, while a separate non-covalent interface is formed by another SARS-CoV-2-specific sequence, 73 YIDI 76 . Together the presence of these interfaces shows how SARS-CoV-2 ORF8 can form unique large-scale assemblies not possible for SARS-CoV, potentially mediating unique immune suppression and evasion activities.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.08.27.270637: (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
    Integrated reflections were scaled, merged and truncated using the CCP4 software suit (20)
    CCP4
    suggested: (CCP4, RRID:SCR_007255)
    Initial phases were obtained for the SeMet dataset using the Phenix autosol pipeline (21).
    Phenix
    suggested: (Phenix, RRID:SCR_014224)
    Iterative rounds of manual model building and refinement were carried out using Coot (23) and Phenix Refine (21) respectively.
    Coot
    suggested: (Coot, RRID:SCR_014222)
    Structural figures were produced using the program PyMOL (https://pymol.org).
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)
    Primary sequence alignment of ORF8 homologs was performed using the ClustalOmega server (24).
    ClustalOmega
    suggested: None

    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: 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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.08.27.270637 on bioRxiv