Receptor binding and proteolysis do not induce large conformational changes in the SARS-CoV spike
Robert N. Kirchdoerfer,
Hannah L. Turner,
Christopher A Cottrell,
Kizzmekia S. Corbett,
Jason S. McLellan,
Andrew B. Ward
Posted 31 Mar 2018
bioRxiv DOI: 10.1101/292672 (published DOI: 10.1038/s41598-018-34171-7)
Posted 31 Mar 2018
Severe acute respiratory syndrome (SARS) coronavirus emerged in 2002 as a highly transmissible pathogenic human betacoronavirus. The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism. As SARS-CoV enters host cells, the viral S undergoes two proteolytic cleavages at S1/S2 and S2′; sites necessary for efficient membrane fusion. Here, we present a cryo-EM analysis of the trimeric SARS-CoV S interactions with ACE2 and of the trypsin-cleaved S. Surprisingly, neither binding to ACE2 nor cleavage by trypsin at the S1/S2 cleavage site impart large conformational changes within S or expose the secondary cleavage site, S2′. These observations suggest that S2′ cleavage does not occur in the S prefusion conformation and that additional triggers may be required.
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