Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2

PLoS Pathog. 2018 Aug 13;14(8):e1007236. doi: 10.1371/journal.ppat.1007236. eCollection 2018 Aug.

Abstract

The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition. Here, we report the structure of the SARS-CoV S glycoprotein in complex with its host cell receptor ACE2 revealed by cryo-electron microscopy (cryo-EM). The complex structure shows that only one receptor-binding domain of the trimeric S glycoprotein binds ACE2 and adopts a protruding "up" conformation. In addition, we studied the structures of the SARS-CoV S glycoprotein and its complexes with ACE2 in different in vitro conditions, which may mimic different conformational states of the S glycoprotein during virus entry. Disassociation of the S1-ACE2 complex from some of the prefusion spikes was observed and characterized. We also characterized the rosette-like structures of the clustered SARS-CoV S2 trimers in the postfusion state observed on electron micrographs. Structural comparisons suggested that the SARS-CoV S glycoprotein retains a prefusion architecture after trypsin cleavage into the S1 and S2 subunits and acidic pH treatment. However, binding to the receptor opens up the receptor-binding domain of S1, which could promote the release of the S1-ACE2 complex and S1 monomers from the prefusion spike and trigger the pre- to postfusion conformational transition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Cryoelectron Microscopy
  • Models, Molecular
  • Peptidyl-Dipeptidase A / chemistry*
  • Peptidyl-Dipeptidase A / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Receptors, Virus / chemistry*
  • Receptors, Virus / metabolism*
  • SARS Virus / chemistry
  • Severe Acute Respiratory Syndrome / virology
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Virus Internalization

Substances

  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2

Grant support

This work was supported by the National Key Plan for Scientific Research and Development of China (2016YFA0501100 and 2016YFD0500307), the National Natural Science Foundation of China (81471929, U1405228 and 31470721) and the Beijing Advanced Innovation Center for Structural Biology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.