Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion

Abstract

Significance The pandemic potential of coronaviruses was recently demonstrated twice by global outbreaks of deadly pneumonia. The spike (S) glycoprotein initiates infection through conformational changes that remain largely uncharacterized. Here we report the cryoEM structure of an S glycoprotein in the postfusion state, showing large-scale rearrangements compared with the prefusion trimer. We further characterized the refolding of the metastable prefusion conformation using limited proteolysis, mass spectrometry, and single-particle EM. The observed similarity to paramyxovirus F structures demonstrates a conserved refolding trajectory and supports the evolutionary relatedness of their fusion subunits. Finally, our data provide a structural framework for understanding antibody neutralization and for engineering vaccines against this medically important virus family.

Keywords

Affiliated Institutions

• Centre National de la Recherche Scientifique FR
• Institut Pasteur FR
• Utrecht University NL
• University of Washington US
• Institut de Virologie FR

Related Publications