Proc Natl Acad Sci U S A . Nanometer-resolution in situ structure of the SARS-CoV-2 postfusion spike protein

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Proc Natl Acad Sci U S A


. 2021 Nov 30;118(48):e2112703118.
doi: 10.1073/pnas.2112703118.
Nanometer-resolution in situ structure of the SARS-CoV-2 postfusion spike protein


Linhua Tai ^{1 2} , Guoliang Zhu ^{1 2} , Minnan Yang ¹ , Lei Cao ¹ , Xiaorui Xing ¹ , Guoliang Yin ^{1 2} , Chun Chan ³ , Chengfeng Qin ⁴ , Zihe Rao ¹ , Xiangxi Wang ^{5 6} , Fei Sun ^{5 2 7 8} , Yun Zhu ⁵



Affiliations

• PMID: 34782481
• DOI: 10.1073/pnas.2112703118

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.

Keywords: SARS-CoV-2; cryo-electron tomography; postfusion state; spike protein; subtomogram analysis.