Structural impact on SARS-CoV-2 spike protein by D614G substitution

  1. Jun Zhang
  2. Yongfei Cai
  3. Tianshu Xiao
  4. Jianming Lu
  5. Hanqin Peng
  6. Sarah M. Sterling
  7. Richard M. Walsh
  8. Sophia Rits-Volloch
  9. Haisun Zhu
  10. Alec N. Woosley
  11. Wei Yang
  12. Piotr Sliz
  13. Bing Chen

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Abstract

Throughout the COVID-19 pandemic, epidemiologists have monitored the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with particular focus on the spike protein. An early variant with an aspartic acid (D) to glycine (G) mutation at position 614, D614G, rapidly became dominant and is maintained in current variants of concern. Zhang et al. investigated the structural basis for the increased spread of this variant, which does so even though it binds less tightly to the host receptor (see the Perspective by Choe and Farzan). Structural and biochemical studies on a full-length G614 spike trimer showed that there are interactions not present in D614 that prevent premature loss of the S1 subunit that binds angiotensin-converting enzyme 2. This stabilization effectively increases the number of spikes that can facilitate infection.

Science , this issue p. 525 ; see also p. 466

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  1. Version published to 10.1126/science.abf2303
  2. Version published to 10.1101/2020.10.13.337980v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.10.13.337980: (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.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Expi293F cells transfected with monomeric ACE2 or dimeric ACE2 expression construct were grown in 250 ml roller bottles with DMEM containing 10% FBS.
    Expi293F
    suggested: RRID:CVCL_D615)
    Briefly, various amount of the full-length SARS-CoV2 (614D or 614G) S construct (0.025-10 μg) and the α fragment of E. coli β-galactosidase construct (10 μg), or the full-length ACE2 construct (10 μg) together with the ω fragment of E. coli β-galactosidase construct (10 μg), were transfected to HEK293T cells using Polyethylenimine (PEI) (80 μg).
    HEK293T
    suggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)
    Software and Algorithms
    SentencesResources
    Automated data collection was carried out using SerialEM version65 36 at a nominal magnification of 105,000× and the K3 detector in counting mode (calibrated pixel size, 0.825 Å) at an exposure rate of ~14.7 electrons per physical pixel per second for the two different detergent samples (14.77 and 14.68, respectively).
    SerialEM
    suggested: (SerialEM, RRID:SCR_017293)
    Local resolution was determined using RELION with half-reconstructions as input maps.
    RELION
    suggested: (RELION, RRID:SCR_016274)
    Iteratively, refinement was performed in both Phenix (real space refinement) and ISOLDE41, and the Phenix refinement strategy included minimization_global, local_grid_search, and adp, with rotamer, Ramachandran, and reference-model restraints, using 6XR8 as the reference model.
    Phenix
    suggested: (Phenix, RRID:SCR_014224)

    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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  4. Version published to 10.1101/2020.10.13.337980v1 on bioRxiv