Distinct conformational states of SARS-CoV-2 spike protein
Yongfei Cai,Yongfei Cai,Jun Zhang,Jun Zhang,Tianshu Xiao,Tianshu Xiao,Hanqin Peng,Sarah M. Sterling,Richard M. Walsh,Shaun Rawson,Sophia Rits-Volloch,Bing Chen,Bing Chen +12 more
TLDR
Two cryo–electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion and postfusion conformations, are reported, advancing the understanding of SARS-CoV-2 entry and may guide the development of vaccines and therapeutics.Abstract:
Intervention strategies are urgently needed to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The trimeric viral spike (S) protein catalyzes fusion between viral and target cell membranes to initiate infection. Here, we report two cryo-electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion (2.9-angstrom resolution) and postfusion (3.0-angstrom resolution) conformations, respectively. The spontaneous transition to the postfusion state is independent of target cells. The prefusion trimer has three receptor-binding domains clamped down by a segment adjacent to the fusion peptide. The postfusion structure is strategically decorated by N-linked glycans, suggesting possible protective roles against host immune responses and harsh external conditions. These findings advance our understanding of SARS-CoV-2 entry and may guide the development of vaccines and therapeutics.read more
Citations
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Antibody-mediated neutralization of SARS-CoV-2
Henning Gruell,Kanika Vanshylla,Timm Weber,Christopher O. Barnes,Christoph Kreer,Florian Klein +5 more
TL;DR: A review of the development, function, and potential use of neutralizing antibodies to prevent and treat CoV-2-associated coronavirus disease 2019 (COVID-19) can be found in this paper .
Journal ArticleDOI
Comparative Perturbation-Based Modeling of the SARS-CoV-2 Spike Protein Binding with Host Receptor and Neutralizing Antibodies: Structurally Adaptable Allosteric Communication Hotspots Define Spike Sites Targeted by Global Circulating Mutations.
TL;DR: In this article, the role of functional residues in the SARS-CoV-2 spike protein was examined using an integrative computational approach to examine molecular mechanisms and determine functional signatures underlying the role in functional residues.
Journal ArticleDOI
Ca2+-dependent mechanism of membrane insertion and destabilization by the SARS-CoV-2 fusion peptide.
TL;DR: In this article, the authors predicted the preferred positions of Ca2+ binding to the SARS-CoV-2-FP, the role of ca2+ ions in mediating peptide-membrane interactions, and the preferred mode of insertion of the Ca2-bound SARS CoV2-2FP, and consequent effects on the lipid bilayer from extensive atomistic molecular dynamics simulations and trajectory analyses.
Journal ArticleDOI
Heterogeneity of Glycan Processing on Trimeric SARS-CoV-2 Spike Protein Revealed by Charge Detection Mass Spectrometry.
Lohra M. Miller,Lauren F. Barnes,Shannon A. Raab,Benjamin E. Draper,Tarick J. El-Baba,Corinne A. Lutomski,Carol V. Robinson,David E. Clemmer,Martin F. Jarrold +8 more
TL;DR: The heterogeneity associated with glycosylation of the 66 N-glycan sites on the protein trimer making up the spike (S) region of the SARS-CoV-2 virus has been assessed by charge detection mass spectrometry.
Journal ArticleDOI
Integrated Biophysical Modeling of the SARS-CoV-2 Spike Protein Binding and Allosteric Interactions with Antibodies.
TL;DR: In this paper, the authors used coevolutionary analysis, molecular simulations, and perturbation-based hierarchical network modeling of SARS-CoV-2 spike protein complexes with a panel of antibodies targeting distinct epitopes to explore molecular mechanisms underlying binding-induced modulation of dynamics and allosteric signaling in the spike proteins.
References
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