Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution
Open Access
- 11 March 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-12
- https://doi.org/10.1038/s41467-021-21767-3
Abstract
In recognizing the host cellular receptor and mediating fusion of virus and cell membranes, the spike (S) glycoprotein of coronaviruses is the most critical viral protein for cross-species transmission and infection. Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. All three receptor-binding domains (RBDs) of these two spike trimers are in the “down” conformation, indicating they are more prone to adopt the receptor-binding inactive state. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. We further identified critical residues in the RBD underlying different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes. These results collectively indicate that tight RBD–ACE2 binding and efficient RBD conformational sampling are required for the evolution of SARS-CoV-2 to gain highly efficient infection.This publication has 48 references indexed in Scilit:
- Quantifying the local resolution of cryo-EM density mapsNature Methods, 2013
- Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi ArabiaThe New England Journal of Medicine, 2012
- Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species TransmissionJournal of Virology, 2010
- PHENIX: a comprehensive Python-based system for macromolecular structure solutionActa crystallographica. Section D, Structural biology, 2010
- MolProbity: all-atom structure validation for macromolecular crystallographyActa crystallographica. Section D, Structural biology, 2009
- EMAN2: An extensible image processing suite for electron microscopyJournal of Structural Biology, 2007
- Automated acquisition of cryo-electron micrographs for single particle reconstruction on an FEI Tecnai electron microscopeJournal of Structural Biology, 2005
- Coot: model-building tools for molecular graphicsActa crystallographica. Section D, Structural biology, 2004
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004
- A Novel Coronavirus Associated with Severe Acute Respiratory SyndromeThe New England Journal of Medicine, 2003