Structural investigation of ACE2 dependent disassembly of the trimeric SARS-CoV-2 Spike glycoprotein
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
The human membrane protein Angiotensin-converting enzyme 2 (hACE2) acts as the main receptor for host cells invasion of the new coronavirus SARS-CoV-2. The viral surface glycoprotein Spike binds to hACE2, which triggers virus entry into cells. As of today, the role of hACE2 for virus fusion is not well understood. Blocking the transition of Spike from its prefusion to post-fusion state might be a strategy to prevent or treat COVID-19. Here we report a single particle cryo-electron microscopy analysis of SARS-CoV-2 trimeric Spike in presence of the human ACE2 ectodomain. The binding of purified hACE2 ectodomain to Spike induces the disassembly of the trimeric form of Spike and a structural rearrangement of its S1 domain to form a stable, monomeric complex with hACE2. This observed hACE2 dependent dissociation of the Spike trimer suggests a mechanism for the therapeutic role of recombinant soluble hACE2 for treatment of COVID-19.
Article activity feed
-
SciScore for 10.1101/2020.10.12.336016: (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. Table 2: Resources
Software and Algorithms Sentences Resources Images were automatically recorded with the SerialEM program (Mastronarde, 2003) at a defocus range of −0.8 ~ −2.5um. SerialEMsuggested: (SerialEM, RRID:SCR_017293)3D references were generated using ab-initio reconstruction (CryoSPARC V2) and followed by two rounds of 3D hetero-refinements. CryoSPARCsuggested: (cryoSPARC, RRID:SCR_016501)For the S1-hACE2 structure, the model was manually docked into the EM density with the program Chimera (Pettersen et al., 2004) and further … SciScore for 10.1101/2020.10.12.336016: (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. Table 2: Resources
Software and Algorithms Sentences Resources Images were automatically recorded with the SerialEM program (Mastronarde, 2003) at a defocus range of −0.8 ~ −2.5um. SerialEMsuggested: (SerialEM, RRID:SCR_017293)3D references were generated using ab-initio reconstruction (CryoSPARC V2) and followed by two rounds of 3D hetero-refinements. CryoSPARCsuggested: (cryoSPARC, RRID:SCR_016501)For the S1-hACE2 structure, the model was manually docked into the EM density with the program Chimera (Pettersen et al., 2004) and further refined using rigid-body fitting in COOT (Emsley et al., 2010). COOTsuggested: (Coot, RRID:SCR_014222)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.
-