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
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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
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Structure and binding properties of Pangolin-CoV spike glycoprotein inform the evolution of SARS-CoV-2.
A.G. Wrobel,D.J. Benton,Pengqi Xu,Pengqi Xu,Lesley J. Calder,Annabel Borg,Chloe Roustan,Stephen R. Martin,Peter B. Rosenthal,John J. Skehel,Steven J. Gamblin +10 more
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Distant residues modulate conformational opening in SARS-CoV-2 spike protein.
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Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models
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Distant Residues Modulate the Conformational Opening in SARS-CoV-2 Spike Protein
TL;DR: This model, based on time-lagged independent component analysis (tICA) and protein graph connectivity network, is able to identify multiple residues that exhibit long-distance coupling with the RBD opening and key non-RBD residues that play a crucial role in spike-receptor binding and infection.
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