ArticlePLoS pathogens2022
Engineered disulfide reveals structural dynamics of locked SARS-CoV-2 spike.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- R1-32-like public antibodies acquire tolerance to SARS-CoV-2 antigenic drift through somatic hypermutation.PLoS biology · 2026Article
- Mass spectrometry-based mapping of conformational epitopes on SARS-CoV-2 antigens targeted by monoclonal antibodies.International journal of biological macromolecules · 2026Article
- Structural basis for sarbecovirus Rc-o319 spike adaptation to Rhinolophus cornutus Bat ACE2 and constraints on switching to human ACE2.PLoS pathogens · 2026Article
- Cryo-EM structure of locked spike glycoprotein from bat SARS-like coronavirus WIV1, molecular dynamics and biophysics across host range.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rewriting the viral script: post-translational modifications orchestrating SARS-CoV-2 pathogenesis and immune evasion.Frontiers in microbiology · 2026Review
- Inactivation of SARS-CoV-2 at acidic pH is driven by partial unfolding of spike.Communications biology · 2025Article
- Structures and receptor binding activities of merbecovirus spike proteins reveal key signatures for human DPP4 adaptation.Science advances · 2025Article
- Modulation of SARS-CoV-2 spike binding to ACE2 through conformational selection.Nature nanotechnology · 2025Article
- SARS-CoV-2 spike protein: structure, viral entry and variants.Nature reviews. Microbiology · 2025Review
- SARS-related coronavirus S-protein structures reveal synergistic RBM interactions underpinning high-affinity human ACE2 binding.Science advances · 2025Article
- Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants.The EMBO journal · 2024Article
- Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein and potentially drive the genesis of Omicron variants.Nature communications · 2024Article
- Evolution at Spike protein position 519 in SARS-CoV-2 facilitated adaptation to humans.Npj viruses · 2024Article
- Assessing pH-Dependent Conformational Changes in the Fusion Peptide Proximal Region of the SARS-CoV-2 Spike Glycoprotein.Viruses · 2024Article
- Enhanced Surface Accessibility of SARS-CoV-2 Omicron Spike Protein Due to an Altered Glycosylation Profile.ACS infectious diseases · 2024Article
- Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.Life science alliance · 2023Article
- Secondary Structures of MERS-CoV, SARS-CoV, and SARS-CoV-2 Spike Proteins Revealed by Infrared Vibrational Spectroscopy.International journal of molecular sciences · 2023Article
- Cryo-EM reveals binding of linoleic acid to SARS-CoV-2 spike glycoprotein, suggesting an antiviral treatment strategy.Acta crystallographica. Section D, Structural biology · 2023Article
- A Tailored Strategy to Crosslink the Aspartate Transcarbamoylase Domain of the Multienzymatic Protein CAD.Molecules (Basel, Switzerland) · 2023Article
- SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope.Nature microbiology · 2022Article
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
Abstract
The spike (S) protein of SARS-CoV-2 has been observed in three distinct pre-fusion conformations: locked, closed and open. Of these, the function of the locked conformation remains poorly understood. Here we engineered a SARS-CoV-2 S protein construct "S-R/x3" to arrest SARS-CoV-2 spikes in the locked conformation by a disulfide bond. Using this construct we determined high-resolution structures confirming that the x3 disulfide bond has the ability to stabilize the otherwise transient locked conformations. Structural analyses reveal that wild-type SARS-CoV-2 spike can adopt two distinct locked-1 and locked-2 conformations. For the D614G spike, based on which all variants of concern were evolved, only the locked-2 conformation was observed. Analysis of the structures suggests that rigidified domain D in the locked conformations interacts with the hinge to domain C and thereby restrains RBD movement. Structural change in domain D correlates with spike conformational change. We propose that the locked-1 and locked-2 conformations of S are present in the acidic high-lipid cellular compartments during virus assembly and egress. In this model, release of the virion into the neutral pH extracellular space would favour transition to the closed or open conformations. The dynamics of this transition can be altered by mutations that modulate domain D structure, as is the case for the D614G mutation, leading to changes in viral fitness. The S-R/x3 construct provides a tool for the further structural and functional characterization of the locked conformations of S, as well as how sequence changes might alter S assembly and regulation of receptor binding domain dynamics.
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