Structural impact on SARS-CoV-2 spike protein by D614G substitution
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Abstract
Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing pandemic, appears to facilitate rapid viral spread. The G614 variant has now replaced the D614-carrying virus as the dominant circulating strain. We report here cryo-EM structures of a full-length S trimer carrying G614, which adopts three distinct prefusion conformations differing primarily by the position of one receptor-binding domain (RBD). A loop disordered in the D614 S trimer wedges between domains within a protomer in the G614 spike. This added interaction appears to prevent premature dissociation of the G614 trimer, effectively increasing the number of functional spikes and enhancing infectivity. The loop transition may also modulate structural rearrangements of S protein required for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.
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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 Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Expi293F cells transfected with monomeric ACE2 or dimeric ACE2 expression construct were grown in 250 ml roller bottles with DMEM containing 10% FBS. Expi293Fsuggested: 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 … 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 Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Expi293F cells transfected with monomeric ACE2 or dimeric ACE2 expression construct were grown in 250 ml roller bottles with DMEM containing 10% FBS. Expi293Fsuggested: 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). HEK293Tsuggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)Software and Algorithms Sentences Resources 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). SerialEMsuggested: (SerialEM, RRID:SCR_017293)Local resolution was determined using RELION with half-reconstructions as input maps. RELIONsuggested: (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. Phenixsuggested: (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.
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