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Nanometer-resolution in situ structure of the SARS-CoV-2 postfusion spike protein

Linhua Tai, Guoliang Zhu, Minnan Yang, Lei Cao, Xiaorui Xing, Guoliang Yin, Chun Chan, Cheng‐Feng Qin, Zihe Rao, Xiangxi Wang, Fei Sun, Yun Zhu

2021Proceedings of the National Academy of Sciences60 citationsDOIOpen Access PDF

Abstract

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates membrane fusion to allow entry of the viral genome into host cells. To understand its detailed entry mechanism and develop a specific entry inhibitor, in situ structural information on the SARS-CoV-2 spike protein in different states is urgent. Here, by using cryo-electron tomography, we observed both prefusion and postfusion spikes in β-propiolactone-inactivated SARS-CoV-2 virions and solved the in situ structure of the postfusion spike at nanometer resolution. Compared to previous reports, the six-helix bundle fusion core, the glycosylation sites, and the location of the transmembrane domain were clearly resolved. We observed oligomerization patterns of the spikes on the viral membrane, likely suggesting a mechanism of fusion pore formation.

Topics & Concepts

BiophysicsLipid bilayer fusionBiologyCoronavirusTransmembrane domainCell biologyTransmembrane proteinProtein structureVirologyCoronavirus disease 2019 (COVID-19)MembraneVirusBiochemistryReceptorDiseaseInfectious disease (medical specialty)MedicinePathologySARS-CoV-2 and COVID-19 ResearchBacteriophages and microbial interactionsLipid Membrane Structure and Behavior
Nanometer-resolution in situ structure of the SARS-CoV-2 postfusion spike protein | Litcius