Structures of SARS-CoV-2 spike protein alert noteworthy sites for the potential approaching variants.
Ontology highlight
ABSTRACT:
SUBMITTER: Xing X
PROVIDER: S-EPMC9642027 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Structures of SARS-CoV-2 spike protein alert noteworthy sites for the potential approaching variants.
Xing Xiaorui X Wang Lei L Cui Zhen Z Fu Wangjun W Zheng Tao T Qin Lili L Ge Pingju P Qian Aidong A Wang Nan N Yuan Shuai S
Virologica Sinica 20221108 6
Similar Datasets
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
Project description: Not available
| EMPIAR-10999 | biostudies-other
Project description: Not available
| S-BSST649 | biostudies-other
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 are 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-EPMC11649927 | biostudies-literature
Project description: Not available
| S-BSST379 | biostudies-other
Project description: Not available
| EMPIAR-10947 | biostudies-other
Project description:SARS-CoV-2 mutations with antigenic effects pose a risk to immunity developed through vaccination and natural infection. While vaccine updates for current variants of concern (VOCs) are underway, it is likewise important to prepare for further antigenic mutations as the virus navigates the heterogeneous global landscape of host immunity. Toward this end, a wealth of data and tools exist that can augment existing genetic surveillance of VOC evolution. In this study, we integrate published datasets describing genetic, structural, and functional constraints on mutation along with computational analyses of antibody-spike co-crystal structures to identify a set of potential antigenic drift sites (PADS) within the receptor binding domain (RBD) and N-terminal domain (NTD) of SARS-CoV-2 spike protein. Further, we project the PADS set into a continuous epitope-paratope space to facilitate interpretation of the degree to which newly observed mutations might be antigenically synergistic with existing VOC mutations, and this representation suggests that functionally convergent and synergistic antigenic mutations are accruing across VOC NTDs. The PADS set and synergy visualization serve as a reference as new mutations are detected on VOCs, enable proactive investigation of potentially synergistic mutations, and offer guidance to antibody and vaccine design efforts.
| S-EPMC8202428 | biostudies-literature
Project description:With the help of novel processing workflows and algorithms, we have obtained a better understanding of the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state. We have re-analyzed previous cryo-EM data combining 3D clustering approaches with ways to explore a continuous flexibility space based on 3D Principal Component Analysis. These advanced analyses revealed a concerted motion involving the receptor-binding domain (RBD), N-terminal domain (NTD), and subdomain 1 and 2 (SD1 & SD2) around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. We show that in this dataset there are not well-defined, stable, spike conformations, but virtually a continuum of states moving in a concerted fashion. We obtained an improved resolution ensemble map with minimum bias, from which we model by flexible fitting the extremes of the change along the direction of maximal variance. Moreover, a high-resolution structure of a recently described biochemically stabilized form of the spike is shown to greatly reduce the dynamics observed for the wild-type spike. Our results provide new detailed avenues to potentially restrain the spike dynamics for structure-based drug and vaccine design and at the same time give a warning of the potential image processing classification instability of these complicated datasets, having a direct impact on the interpretability of the results.
| S-EPMC7359526 | biostudies-literature
Project description:Using a new consensus-based image-processing approach together with principal component analysis, the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state have been analysed. These studies revealed concerted motions involving the receptor-binding domain (RBD), N-terminal domain, and subdomains 1 and 2 around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. It is shown that in this data set there are not well defined, stable spike conformations, but virtually a continuum of states. An ensemble map was obtained with minimum bias, from which the extremes of the change along the direction of maximal variance were modeled by flexible fitting. The results provide a warning of the potential image-processing classification instability of these complicated data sets, which has a direct impact on the interpretability of the results.
| S-EPMC7553147 | biostudies-literature
Project description:The severe acute respiratory syndrome spread worldwide, causing a pandemic. SARS-CoV-2 mutations have arisen in the spike, a glycoprotein at the viral envelope and an antigenic candidate for vaccines against COVID-19. Here, we present comparative data of the glycosylated full-length ancestral and D614G spike together with three other transmissible strains classified by the World Health Organization as variants of concern: beta, gamma, and delta. By showing that D614G has less hydrophobic surface exposure and trimer persistence, we place D614G with features that support a model of temporary fitness advantage for virus spillover. Furthermore, during the SARS-CoV-2 adaptation, the spike accumulates alterations leading to less structural stability for some variants. The decreased trimer stability of the ancestral and gamma and the presence of D614G uncoupled conformations mean higher ACE-2 affinities compared to the beta and delta strains. Mapping the energetics and flexibility of variants is necessary to improve vaccine development.
| S-EPMC9710096 | biostudies-literature