SARS-CoV-2 spike protein fusion transformation
This page is under construction starting August 3, 2020.
The spike protein of SARS-CoV-2 plays a central role in coronavirus attachment to the ACE2 receptor on host cells, and in getting the RNA genome of the virus into the host cell via fusion of the virus and host cell membranes, initiating infection.
SARS-CoV-2 spike protein undergoes a dramatic conformational rearrangement that plays a central role in fusing the coronavirus membrane with the host cell membrane[1]. Similar conformational transformations have been observed for the spike protein of SARS-CoV[2] and mouse hepatitis virus[3], among others. These rearrangements also have much in common with the membrane fusion mechansism of influenza hemagglutinin[4]. The molecular scenes in this article are based on the cryo-EM pre- and post-fusion structures of SARS-CoV-2 reported July, 2020, by Cai, Zhang and coworkers with the group of Bing Chen[1].
The is a homo-trimer, each chain having a mature length of 1,261 amino acids. This pre-fusion cryo-EM structure 6xr8 is complete except for 110 residues of the C-terminus, comprising 48 residues of the stem (heptad repeat 2 domain), a 23-residue trans-membrane domain, and a 39 residue cytoplasmic domain.
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ReferencesReferences
- ↑ 1.0 1.1 Cai Y, Zhang J, Xiao T, Peng H, Sterling SM, Walsh RM Jr, Rawson S, Rits-Volloch S, Chen B. Distinct conformational states of SARS-CoV-2 spike protein. Science. 2020 Jul 21. pii: science.abd4251. doi: 10.1126/science.abd4251. PMID:32694201 doi:http://dx.doi.org/10.1126/science.abd4251
- ↑ Fan X, Cao D, Kong L, Zhang X. Cryo-EM analysis of the post-fusion structure of the SARS-CoV spike glycoprotein. Nat Commun. 2020 Jul 17;11(1):3618. doi: 10.1038/s41467-020-17371-6. PMID:32681106 doi:http://dx.doi.org/10.1038/s41467-020-17371-6
- ↑ Walls AC, Tortorici MA, Snijder J, Xiong X, Bosch BJ, Rey FA, Veesler D. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11157-11162. doi:, 10.1073/pnas.1708727114. Epub 2017 Oct 3. PMID:29073020 doi:http://dx.doi.org/10.1073/pnas.1708727114
- ↑ Pabis A, Rawle RJ, Kasson PM. Influenza hemagglutinin drives viral entry via two sequential intramembrane mechanisms. Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7200-7207. doi:, 10.1073/pnas.1914188117. Epub 2020 Mar 18. PMID:32188780 doi:http://dx.doi.org/10.1073/pnas.1914188117