Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structures and distributions of SARS-CoV-2 spike proteins on intact virions.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude¹. Heavily glycosylated S trimers bind to the angiotensin-converting enzyme 2 receptor and mediate entry of virions into target cells^2-6. S exhibits extensive conformational flexibility: it modulates exposure of its receptor-binding site and subsequently undergoes complete structural rearrangement to drive fusion of viral and cellular membranes^2,7,8. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy^2,7,9-12, but the structure and distribution of S on the virion surface remain unknown. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions and determine the high-resolution structure, conformational flexibility and distribution of S trimers in situ on the virion surface. These results reveal the conformations of S on the virion, and provide a basis from which to understand interactions between S and neutralizing antibodies during infection or vaccination.

SUBMITTER: Ke Z

PROVIDER: S-EPMC7116492 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Cryo-EM structure of SARS-CoV-2 Spike Proteins on intact virions

Project description: Not available

| EMPIAR-10492 | biostudies-other

Subtomogram averaging and classification of SARS-CoV-2 Spike Proteins on intact virions

Project description: Not available

| EMPIAR-10493 | biostudies-other

Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions.

Project description:Antibody neutralization is an important prognostic factor in many viral diseases. To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal MLV genome encoding firefly luciferase. These pseudovirions provide a practical means of assessing immune responses under laboratory conditions consistent with biocontainment level 2.

| S-EPMC7523104 | biostudies-literature

Secondary Structures of MERS-CoV, SARS-CoV, and SARS-CoV-2 Spike Proteins Revealed by Infrared Vibrational Spectroscopy.

Project description:All coronaviruses are characterized by spike glycoproteins whose S1 subunits contain the receptor binding domain (RBD). The RBD anchors the virus to the host cellular membrane to regulate the virus transmissibility and infectious process. Although the protein/receptor interaction mainly depends on the spike's conformation, particularly on its S1 unit, their secondary structures are poorly known. In this paper, the S1 conformation was investigated for MERS-CoV, SARS-CoV, and SARS-CoV-2 at serological pH by measuring their Amide I infrared absorption bands. The SARS-CoV-2 S1 secondary structure revealed a strong difference compared to those of MERS-CoV and SARS-CoV, with a significant presence of extended β-sheets. Furthermore, the conformation of the SARS-CoV-2 S1 showed a significant change by moving from serological pH to mild acidic and alkaline pH conditions. Both results suggest the capability of infrared spectroscopy to follow the secondary structure adaptation of the SARS-CoV-2 S1 to different environments.

| S-EPMC10253540 | biostudies-literature

Molecular dynamics simulations explore effects of electric field orientations on spike proteins of SARS-CoV-2 virions.

Project description:Emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its current worldwide spread have caused a pandemic of acute respiratory disease COVID-19. The virus can result in mild to severe, and even to fatal respiratory illness in humans, threatening human health and public safety. The spike (S) protein on the surface of viral membrane is responsible for viral entry into host cells. The discovery of methods to inactivate the entry of SARS-CoV-2 through disruption of the S protein binding to its cognate receptor on the host cell is an active research area. To explore other prevention strategies against the quick spread of the virus and its mutants, non-equilibrium molecular dynamics simulations have been employed to explore the possibility of manipulating the structure-activity of the SARS-CoV-2 spike glycoprotein by applying electric fields (EFs) in both the protein axial directions and in the direction perpendicular to the protein axis. We have found out the application of EFs perpendicular to the protein axis is most effective in denaturing the HR2 domain which plays critical role in viral-host membrane fusion. This finding suggests that varying irradiation angles may be an important consideration in developing EF based non-invasive technologies to inactivate the virus.

| S-EPMC9334739 | biostudies-literature

Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants

Project description:The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins, which are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S protein from SARS-CoV-2 variants has revealed this structural adaptation at high resolution. The analysis of S trimers in situ on intact virions has the potential to provide more functionally relevant insights into S structure and virion morphology. Here, we characterized B.1, Alpha, Beta, Gamma, Delta, Kappa, and Mu variants by cryo-electron microscopy and tomography, assessing S cleavage, virion morphology, S incorporation, "in-situ" high-resolution S structures and the range of S conformational states. We found no evidence for adaptive changes in virion morphology, but describe multiple different positions in the S protein where amino acid changes alter local protein structure. Taken together, our data is consistent with a model where amino acid changes at multiple positions from the top to the base of the spike cause structural changes that can modulate the conformational dynamics of the S protein.

| S-SCDT-10_1038-S44318-024-00303-1 | biostudies-other

Topography, Spike Dynamics, and Nanomechanics of Individual Native SARS-CoV-2 Virions.

Project description:SARS-CoV-2, the virus responsible for the current COVID-19 pandemic, displays a corona-shaped layer of spikes which play a fundamental role in the infection process. Recent structural data suggest that the spikes possess orientational freedom and the ribonucleoproteins segregate into basketlike structures. How these structural features regulate the dynamic and mechanical behavior of the native virion are yet unknown. By imaging and mechanically manipulating individual, native SARS-CoV-2 virions with atomic force microscopy, here, we show that their surface displays a dynamic brush owing to the flexibility and rapid motion of the spikes. The virions are highly compliant and able to recover from drastic mechanical perturbations. Their global structure is remarkably temperature resistant, but the virion surface becomes progressively denuded of spikes upon thermal exposure. The dynamics and the mechanics of SARS-CoV-2 are likely to affect its stability and interactions.

| S-EPMC7839418 | biostudies-literature

Supramolecular Organization of SARS-CoV and SARS-CoV-2 Virions Revealed by Coarse-Grained Models of Intact Virus Envelopes.

Project description:The coronavirus disease 19 (COVID-19) pandemic is causing a global health crisis and has already caused a devastating societal and economic burden. The pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a high sequence and architecture identity with SARS-CoV, but far more people have been infected by SARS-CoV-2. Here, combining the structural data from cryo-electron microscopy and structure prediction, we constructed bottom-up Martini coarse-grained models of intact SARS-CoV and SARS-CoV-2 envelopes. Microsecond molecular dynamics simulations were performed, allowing us to explore their dynamics and supramolecular organization. Both SARS-CoV and SARS-CoV-2 envelopes present a spherical morphology, with structural proteins forming multiple string-like islands in the membrane and clusters between the heads of spike proteins. Critical differences between the SARS-CoV and SARS-CoV-2 envelopes are the interaction pattern between the spike proteins and the flexibility of the spike proteins. Our models provide structural and dynamic insights into the SARS virus envelopes and could be used for further investigation, such as drug design and membrane fusion and fission processes.

| S-EPMC8691453 | biostudies-literature

Structures from "Engineering Neutralizing SARS-CoV Antibodies to Bind SARS-CoV-2"

Project description: Not available

| S-BSST379 | biostudies-other

SARS-CoV-2 S Omicron Spike B.1.1.529

Project description: Not available

| EMPIAR-10947 | biostudies-other