SARS-CoV-2 spike protein fusion transformation

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Revision as of 16:36, 5 August 2020

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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 spike protein reported July, 2020, by Cai, Zhang and coworkers with the group of Bing Chen^[1].

Click the green links below to change the molecular scene. Drag to rotate. Zoom the molecule with your mouse wheel, or Shift-Drag up/down.

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 (narrow end), comprising 48 residues of the stem (heptad repeat 2 domain), a 23-residue trans-membrane domain, and a 39 residue cytoplasmic domain.

as in Cai, Zhang et al. ^[1] (lengths):

14-306 (293): N-terminal domain.
307-330 (24): Linker.
331-528 (198): Receptor binding domain, binds to angiotensin converting enzyme 2 (ACE2).
529-591 (63): CTD1 (C terminal region of S1 fragment after furin cleavage).
592-676 (85): CTD2 (C terminus of S1 fragment after furin cleavage).
677-688 (12): Pink balls mark the furin cleavage site PRRAR (missing in this model due to disorder).
689-816 (128): Linker
817-825 (9): Fusion peptide (FP).
826-834 (9): Fusion peptide proximal region (FPPR).
835-910 (76): Linker
911-985 (75): Heptad repeat 1 (HR1)
986-1035 (49): Central helix (CH)
1036-1068 (33): Connector domain (CD)
1069-1162 (93): Linker
1163-1273 (111): Missing in this model due to disorder. Stem, transmembrane domain, cytoplasmic domain.

It will be easier to see the domains if you look at only one of the three chains:

A protease, typically furin, cuts the chains at the position marked with Pink balls, but the assembly, now six chains, remains intact. The cut may facilitate extending one receptor binding domain to engage the ACE2 receptor. The cut divides each chain of protein S into an N-terminal S1 receptor-binding fragment, and a C-terminal S2 fusion fragment^[1]. , will later separate.

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 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

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Eric Martz, Karsten Theis

Retrieved from "http://52.214.119.220/wiki/index.php/SARS-CoV-2_spike_protein_fusion_transformation"

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-A protease, typically [[furin]], cuts the chains at the position marked with <b><font color="#ff8080">Pink balls</font></b>, but the assembly, now six chains, remains intact. The cut may facilitate [[SARS-CoV-2 spike protein priming by furin|extending one receptor binding domain]] to engage the ACE2 receptor. The cut divides each chain of protein S into an N-terminal '''S1''' region, and a C-terminal '''S2''' region. <scene name='85/857791/Pre-fusion_6xr8/5'>S1, here shown translucent</scene>, will later separate.
+A protease, typically [[furin]], cuts the chains at the position marked with <b><font color="#ff8080">Pink balls</font></b>, but the assembly, now six chains, remains intact. The cut may facilitate [[SARS-CoV-2 spike protein priming by furin|extending one receptor binding domain]] to engage the ACE2 receptor. The cut divides each chain of protein S into an N-terminal '''S1''' receptor-binding fragment, and a C-terminal '''S2''' fusion fragment<ref name="cai-zhang" />. <scene name='85/857791/Pre-fusion_6xr8/5'>S1, here shown translucent</scene>, will later separate.
 </StructureSection>
 == References ==
 <references/>

SARS-CoV-2 spike protein fusion transformation

From Proteopedia

Revision as of 16:36, 5 August 2020

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