Sandbox Reserved 1849
From Proteopedia
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====Structure And Function==== | ====Structure And Function==== | ||
| - | <p>The <scene name='10/1075251/Spike_protein_closed_spacefill/2'>spike protein</scene> of SARS-COV-2 is a symmetric trimer featuring 3 spike glycoprotein chains (UNIPROT: [https://www.uniprot.org/uniprotkb/P0DTC2/entry P0DTC2]). Each monomer of the spike is called a spike glycoprotein, and it contains 2 main parts: The S1 and S2 subunits<ref name="Huang"></ref>. However, the native spike protein does not exist in this state prior to infection. The protein is actually inactive initially, but is later activated by proteases cleaving the inactive S protein into its two active subunits<ref name="Huang"></ref>. The S1 subunit contains the N-Terminal domain (NTD), C-Terminal Domain (CRD), and the Receptor Binding Domain (RBD). The RBD is responsible for binding to the ACE2 receptor on the surface of the target cell, as well as neutralizing antibodies. The NTD, CTD, and their relevant interfaces actually play much larger roles in the binding of the spike protein to ACE2 than the RBD does due to their larger surface areas<ref name="Huang"></ref>. The S2 subunit is responsible for viral fusion and entry. Once bound to ACE2, and after the different domains in S2 have anchored to the membrane as well as delivered the viral envelope, the the S2 subunit changes conformation from the pre-hairpin to postfusion-hairpin conformation<ref name="Huang"></ref>. | + | <p>The <scene name='10/1075251/Spike_protein_closed_spacefill/2'>spike protein</scene> of SARS-COV-2 is a symmetric trimer featuring 3 spike glycoprotein chains (UNIPROT: [https://www.uniprot.org/uniprotkb/P0DTC2/entry P0DTC2]). Each monomer of the spike is called a spike glycoprotein, and it contains 2 main parts: The S1 and S2 subunits<ref name="Huang">DOI:10.1038/s41401-020-0485-4</ref>. However, the native spike protein does not exist in this state prior to infection. The protein is actually inactive initially, but is later activated by proteases cleaving the inactive S protein into its two active subunits<ref name="Huang">DOI:10.1038/s41401-020-0485-4</ref>. The S1 subunit contains the N-Terminal domain (NTD), C-Terminal Domain (CRD), and the Receptor Binding Domain (RBD). The RBD is responsible for binding to the ACE2 receptor on the surface of the target cell, as well as neutralizing antibodies. The NTD, CTD, and their relevant interfaces actually play much larger roles in the binding of the spike protein to ACE2 than the RBD does due to their larger surface areas<ref name="Huang">DOI:10.1038/s41401-020-0485-4</ref>. The S2 subunit is responsible for viral fusion and entry. Once bound to ACE2, and after the different domains in S2 have anchored to the membrane as well as delivered the viral envelope, the the S2 subunit changes conformation from the pre-hairpin to postfusion-hairpin conformation<ref name="Huang">DOI:10.1038/s41401-020-0485-4</ref>. |
| - | Throughout the entire process, the spike protein has 3 main conformations. An <scene name='10/1075251/Spike_protein_closed_spacefill/3'>inactive, "closed"</scene> conformation; an active, "open" conformation; and a <scene name='10/1075251/Spike_protein_postfusion/1'>post-fusion hairpin</scene> conformation mentioned previously<ref name="Huang"></ref><ref name="Yuan"></ref><ref name="Zhang"></ref>. In the closed conformation, the RBDs of each monomer are tucked inwards, preventing interaction. In the open conformation, however, 1 or more of these RBDs can be in the "up" conformation, meaning they are exposed and able to interact within the extracellular space. Mainly, there exits a "<scene name='10/1075251/Spike_protein_1-up_yang/1'>1-up</scene>" and "<scene name='10/1075251/Spike_protein_2-up_yang/2'>2-up</scene>" conformation in this phase<ref name="Yuan"></ref>. | + | Throughout the entire process, the spike protein has 3 main conformations. An <scene name='10/1075251/Spike_protein_closed_spacefill/3'>inactive, "closed"</scene> conformation; an active, "open" conformation; and a <scene name='10/1075251/Spike_protein_postfusion/1'>post-fusion hairpin</scene> conformation mentioned previously<ref name="Huang">DOI:10.1038/s41401-020-0485-4</ref></ref><ref name="Yuan">PMID:28393837</ref><ref name="Zhang">PMID:34534731</ref>. In the closed conformation, the RBDs of each monomer are tucked inwards, preventing interaction. In the open conformation, however, 1 or more of these RBDs can be in the "up" conformation, meaning they are exposed and able to interact within the extracellular space. Mainly, there exits a "<scene name='10/1075251/Spike_protein_1-up_yang/1'>1-up</scene>" and "<scene name='10/1075251/Spike_protein_2-up_yang/2'>2-up</scene>" conformation in this phase<ref name="Yuan">PMID:28393837</ref><ref name="Zhang">PMID:34534731</ref>. |
</p> | </p> | ||
====Function==== | ====Function==== | ||
Revision as of 17:59, 3 April 2025
| This Sandbox is Reserved from March 18 through September 1, 2025 for use in the course CH462 Biochemistry II taught by R. Jeremy Johnson and Mark Macbeth at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1828 through Sandbox Reserved 1846. |
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SARS-COV2 Minibinders
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References
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020 Sep;41(9):1141-1149. doi: 10.1038/s41401-020-0485-4., Epub 2020 Aug 3. PMID:32747721 doi:http://dx.doi.org/10.1038/s41401-020-0485-4
- ↑ 4.0 4.1 4.2 Yuan Y, Cao D, Zhang Y, Ma J, Qi J, Wang Q, Lu G, Wu Y, Yan J, Shi Y, Zhang X, Gao GF. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains. Nat Commun. 2017 Apr 10;8:15092. doi: 10.1038/ncomms15092. PMID:28393837 doi:http://dx.doi.org/10.1038/ncomms15092
- ↑ 5.0 5.1 5.2 Zhang J, Xiao T, Cai Y, Chen B. Structure of SARS-CoV-2 spike protein. Curr Opin Virol. 2021 Oct;50:173-182. PMID:34534731 doi:10.1016/j.coviro.2021.08.010
