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TitleCryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2.
Journal, issue, pagesPLoS Pathog, Vol. 14, Issue 8, Page e1007236, Year 2018
Publish dateAug 13, 2018
AuthorsWenfei Song / Miao Gui / Xinquan Wang / Ye Xiang /
PubMed AbstractThe 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 ...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.
External linksPLoS Pathog / PubMed:30102747 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 30.5 Å
Structure data

EMDB-9583:
Trypsin-cleaved SARS-CoV spike glycoprotein and ACE2 complex, ACE2-free conformation with three RBD in down position
Method: EM (single particle) / Resolution: 8.3 Å

EMDB-9584:
Trypsin-cleaved SARS-CoV spike glycoprotein and ACE2 complex, ACE2-free conformation with one RBD in up position
Method: EM (single particle) / Resolution: 9.0 Å

EMDB-9585:
Trypsin-cleaved SARS-CoV spike glycoprotein and ACE2 complex, ACE2-bound conformation 1
Method: EM (single particle) / Resolution: 19.7 Å

EMDB-9586:
Trypsin-cleaved SARS-CoV spike glycoprotein and ACE2 complex, ACE2-bound conformation 2
Method: EM (single particle) / Resolution: 9.0 Å

EMDB-9587:
Trypsin-cleaved SARS-CoV spike glycoprotein and ACE2 complex, ACE2-bound conformation 3
Method: EM (single particle) / Resolution: 18.5 Å

EMDB-9588, PDB-6acc:
Trypsin-cleaved and low pH-treated SARS-CoV spike glycoprotein and ACE2 complex, ACE2-free conformation with three RBD in down conformation
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-9589, PDB-6acd:
Trypsin-cleaved and low pH-treated SARS-CoV spike glycoprotein and ACE2 complex, ACE2-free conformation with one RBD in up conformation
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-9591, PDB-6acg:
Trypsin-cleaved and low pH-treated SARS-CoV spike glycoprotein and ACE2 complex, ACE2-bound conformation 1
Method: EM (single particle) / Resolution: 5.4 Å

EMDB-9593, PDB-6acj:
Trypsin-cleaved and low pH-treated SARS-CoV spike glycoprotein and ACE2 complex, ACE2-bound conformation 2
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-9594, PDB-6ack:
Trypsin-cleaved and low pH-treated SARS-CoV spike glycoprotein and ACE2 complex, ACE2-bound conformation 3
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-9595:
Trypsin-cleaved SARS-CoV spike glycoprotein
Method: EM (single particle) / Resolution: 6.8 Å

EMDB-9596:
Trypsin-cleaved and low pH-treated SARS-CoV spike glycoprotein
Method: EM (single particle) / Resolution: 6.7 Å

EMDB-9597:
Postfusion state of SARS-CoV spike glycoprotein
Method: EM (single particle) / Resolution: 30.5 Å

EMDB-9598:
Trypsin-cleaved and low pH-treated SARS-CoV spike glycoprotein and ACE2 complex, dissociated S1-ACE2
Method: EM (single particle) / Resolution: 11.6 Å

Source
  • SARS coronavirus
  • homo sapiens (human)
  • human sars coronavirus
KeywordsVIRAL PROTEIN / SARS-CoV / spike / glycoprotein / Class I fusion protein / membrane fusion / VIRAL PROTEIN/HYDROLASE / VIRAL PROTEIN-HYDROLASE complex

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