Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2

By Wenfei Song, M. Gui, Xinquan Wang, Y. Xiang. PLoS Pathogens, 2018

806 citations recorded by the source corpus.

The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition. Here, we report the structure of the SARS-CoV S glycoprotein in complex with its host cell receptor ACE2 revealed by cryo-electron microscopy (cryo-EM). The complex structure shows that only one receptor-binding domain of the trimeric S glycoprotein binds ACE2 and adopts a protruding “up” conformation. In addition, we studied the structures of the SARS-CoV S glycoprotein and its complexes with ACE2 in different in vitro conditions, which may mimic different conformational states of the S glycoprotein during virus entry. Disassociation of the S1-ACE2 complex from some of the prefusion spikes was observed and characterized. We also characterized the rosette-like structures of the clustered SARS-CoV S2 trimers in the postfusion state observed on electron micrographs. Structural comparisons suggested that the SARS-CoV S glycoprotein retains a prefusion architecture after trypsin cleavage into the S1 and S2 subunits and acidic pH treatment. However, binding to the receptor opens up the receptor-binding domain of S1, which could promote the release of the S1-ACE2 complex and S1 monomers from the prefusion spike and trigger the pre- to postfusion conformational transition.

Subfields: Animal Science and Zoology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/e0f1b5a380193e6ff0a4de4d44d74ad309a5dda3

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In Animal Science and Zoology

1. D. Veesler
2. A. Walls
3. M. A. Tortorici
4. J. Shang
5. Yushun Wan
6. A. Tortoricia
7. David Veeslera
8. Fang Li

In Infectious Diseases

1. D. Veesler
2. A. Walls
3. M. A. Tortorici
4. J. Shang
5. Yushun Wan
6. Q. Geng
7. A. Tortoricia
8. David Veeslera

Citations in the corpus

• Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry (2019, background): “223 However, based on previous studies, the receptor-binding site on the RBD in the spike 224 trimer is only accessible when the RBD is in the standing-up position (18, 20, 21).”
• Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, positive): “…with previous reports of the SARS-CoV neutralizing mAb S230-and ACE2-mediated transition of SARS-CoV S from the prefusion to the postfusion states (Song et al., 2018; Walls et al., 2019), the cryo-EM observation of S 1 subunit trimers released from the MERS-CoV S ectodomain upon cleavage at S 1…”
• The enemy who sealed the world: effects quarantine due to the COVID-19 on sleep quality, anxiety, and psychological distress in the Italian population (2020, positive): “Due to the limited resolution of negative-stain EM, we could not clearly see the conformation of the Fab-bound RBD. However, based on previous studies, the receptor-binding site on the RBD in the spike trimer is accessible only when the RBD is in the standing-up position (18, 20, 21) .”
• Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient (2020, neutral): “RBD, ACE2, Spike ectodomain and CR3022 cloning Constructs are as described by Huo et al12.”
• The human coronavirus HCoV-229E S-protein structure and receptor binding (2019, background): “741 Two views showing a morphing between the two S-proteins.”
• Characterization of neutralizing antibodies from a SARS-CoV-2 infected individual (2020, result): “High resolution structures of the SARS-CoV-2 prefusion-stabilized spike (S) ectodomain revealed that it adopts multiple conformations with either one receptor binding domain (RBD) in the “up” or “open” conformation or all RBDs in the “down” or “closed” conformation, similar to previous reports on bo”
• The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status (2020, background): “Structure of the SARS-CoV-2 Spike in the prefusion conformation [38].”
• Controlling the SARS-CoV-2 spike glycoprotein conformation (2020, neutral): “We collected cryo-EM datasets for the rS2d and u1S2q constructs (Figures 2–6, Table 1, Extended Data Figures 5–9).”
• Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein (2020, methodology): “As is the case for other b-coronavirus S glycoproteins, including SARS-CoV S (Gui et al., 2017; Kirchdoerfer et al., 2018; Pallesen et al., 2017; Park et al., 2019; Song et al., 2018; Tortorici et al., 2019;Walls et al., 2016a;Walls et al., 2016b;Walls et al., 2019; Yuan et al., 2017), the S1 subuni”
• Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike (2020, neutral): “The RBD is predominantly in a 'down' state where the receptor binding site is inaccessible, however it appears that it stochastically flips up with a hinge-like motion transiently presenting the ACE2 receptor binding site (Roy, 2020; Song et al., 2018; Walls et al., 2020; Wrapp et al., 2020) .”