SARS-CoV-2 spike protein fusion transformation
From Proteopedia
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A protease, typically [[furin]], cuts the chains at the position marked with <b><font color="#ff8080">Pink balls</font></b><ref name="cut1" />, 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. | A protease, typically [[furin]], cuts the chains at the position marked with <b><font color="#ff8080">Pink balls</font></b><ref name="cut1" />, 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. | ||
| - | Binding to ACE2 and a second proteolytic cut are believed to trigger release of S1 | + | Binding to ACE2 and a second proteolytic cut are believed to trigger release of S1<ref name="cai-zhang" />, after which only S2 remains attached to the virus membrane through the stem and transmembrane domains (absent in this model) that extend from the <font color="red">'''red balls'''</font>. |
</StructureSection> | </StructureSection> | ||
Revision as of 19:21, 5 August 2020
This page is under construction starting August 3, 2020. This red text will be removed when the page is completed.
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.
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See Also
Methods
The pre-fusion structure 6xr8 was morphed to the post-fusion structure 6xra by linear interpolation, requesting 14 intermediate frames (16 total), using the server provided by Karsten Theis after another method[6] gave unsatisfactory results. This produced an 11 MB file, which took 25 sec to load into JSmol. Each script took a minimum of 8 sec to complete. To reduce both the bulk of this file and the processing times for JSmol, the alpha carbons were extracted (along with the MODEL and ENDMDL records) by deleting all other lines in the PDB file[7]. The resulting 16 model morph PDB file is Image:Morf-6xr8-6xra-theis-cao.pdb.
References and Notes
- ↑ 1.0 1.1 1.2 1.3 1.4 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
- ↑ 5.0 5.1 According to Cai, Zhang et al. (their Fig. 4), the initial cut by furin occurs between Arg685 and Ser686 at * in the sequence PRRAR*SVASQ. Thus, S1 is 13-685 (length 673, excluding a 12 residue signal sequence), or 53% of the original chain, leaving S2 as 686-1273, length 588, 47%.
- ↑ Proteopedia's PyMOL morph server was used in both RigiMOL and linear modes, all atoms or only alpha carbon atoms. Rendering these as backbones or traces by Jmol gave broken lines. The reason for backbone breaking was not investigated further.
- ↑ BBEdit (barebones.com) has a regular expression "grep" mode that was used to delete unwanted lines. Deletion was done by find and replace with nothing. First, REMARK lines were deleted by finding ^REMARK.*\n, and similarly HETATM lines. Finally, non-CA ATOM lines were found with ^ATOM [ \d]\d\d\d\d [NCOS][ B-Z].*\n, leaving ATOM CA lines, MODEL and ENDMDL lines. This strategy was used after two other strategies failed. Selecting *.ca in the Jmol Java application and saving them produced a PDB file with numerous errors. I was unable to get regular expression alternation to work in either macOS Darwin sed, or GNU sed, thus unable to extract the desired 3 line types with "sed -n /match1|match2|match3/p". I was also unable to get BBEdit to delete lines not containing a specified string, e.g. find (?!MODEL).
