Distinct conformational states of SARS-CoV-2 spike protein

Science. 2020 Sep 25;369(6511):1586-1592. doi: 10.1126/science.abd4251. Epub 2020 Jul 21.

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.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Cryoelectron Microscopy
  • HEK293 Cells
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Peptidyl-Dipeptidase A / chemistry
  • Protein Domains
  • Protein Multimerization
  • Protein Structure, Secondary
  • Receptors, Virus / chemistry
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Virus Internalization

Substances

  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2