SARS-CoV-2 protein S

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
<SX viewer='molstar' load='' size='340' side='right' caption='' scene=''>
 
-
{{Theoretical_model}}
 
-
== Function ==
 
-
'''Surface glycoprotein (S)'''
 
-
Spike protein S1 (residue 14-685): attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.
 
-
Spike protein S2 (residue 686-1273): mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.
 
-
Spike protein S2' (residue 816-1273): acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.<ref>[https://zhanglab.ccmb.med.umich.edu/COVID-19/ Modeling of the SARS-COV-2 Genome]</ref><ref>pmid 32200634</ref>
 
- 
- 
==Spike Glycoprotein==
==Spike Glycoprotein==
 +
<StructureSection load='6vsb' size='350' side='right' caption='Cryo-EM reconstruction of the spike. It consists of 3 monomers of the Spike glycoprotein (pdb code 6vsb)'>
 +
==Function==
The homotrimeric spike glycoprotein on the virus envelope mediates the entry into cell. Every monomer consists of the two subunits S1 and S2. SARS-CoV-2 spike S1 subunit binds the cellular receptor called angiotensin converting enzyme 2 (ACE2). Binding triggers a cascade of events leading to the fusion of cell and virus membrane. After the prefusion trimer is destabilized, the S1 subunit is shedded leading to transition of the S2 subunit to a stable postfusion conformation. To engage a host cell receptor, the receptor-binding domain (RBD) of S1 undergoes hinge-like conformational rearrangement that transiently hide or expose the residues necessary for receptor binding. <ref name="Wrapp"> Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola et al. (2020): Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. In: Science 367 (6483), S. 1260–1263. DOI: 10.1126/science.abb2507.</ref>
The homotrimeric spike glycoprotein on the virus envelope mediates the entry into cell. Every monomer consists of the two subunits S1 and S2. SARS-CoV-2 spike S1 subunit binds the cellular receptor called angiotensin converting enzyme 2 (ACE2). Binding triggers a cascade of events leading to the fusion of cell and virus membrane. After the prefusion trimer is destabilized, the S1 subunit is shedded leading to transition of the S2 subunit to a stable postfusion conformation. To engage a host cell receptor, the receptor-binding domain (RBD) of S1 undergoes hinge-like conformational rearrangement that transiently hide or expose the residues necessary for receptor binding. <ref name="Wrapp"> Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola et al. (2020): Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. In: Science 367 (6483), S. 1260–1263. DOI: 10.1126/science.abb2507.</ref>
Line 31: Line 24:
Coronavirus spike proteins are densely decorated by heterogenous N-linked glycans protruding from the trimer surface. SARS-CoV-2 S comprises 22 N-linked glycosylation sequons per protomer. N-linked glycans play a key role in proper protein folding and in priming by host proteases <ref> Walls, Alexandra C.; Park, Young-Jun; Tortorici, M. Alejandra; Wall, Abigail; McGuire, Andrew T.; Veesler, David (2020): Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. In: Cell. DOI: 10.1016/j.cell.2020.02.058.</ref> Since glycans can shield the amino acid residues and other epitopes from cells and antibody recognition, glycosylation can enable the coronavirus to evade both the innate and adaptive immune responses. <ref name="Lan" /> <ref>Shen, Shuo; Tan, Timothy H. P.; Tan, Yee-Joo (2007): Expression, glycosylation, and modification of the spike (S) glycoprotein of SARS CoV. In: Methods in molecular biology (Clifton, N.J.) 379, S. 127–135. DOI: 10.1007/978-1-59745-393-6_9.</ref>
Coronavirus spike proteins are densely decorated by heterogenous N-linked glycans protruding from the trimer surface. SARS-CoV-2 S comprises 22 N-linked glycosylation sequons per protomer. N-linked glycans play a key role in proper protein folding and in priming by host proteases <ref> Walls, Alexandra C.; Park, Young-Jun; Tortorici, M. Alejandra; Wall, Abigail; McGuire, Andrew T.; Veesler, David (2020): Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. In: Cell. DOI: 10.1016/j.cell.2020.02.058.</ref> Since glycans can shield the amino acid residues and other epitopes from cells and antibody recognition, glycosylation can enable the coronavirus to evade both the innate and adaptive immune responses. <ref name="Lan" /> <ref>Shen, Shuo; Tan, Timothy H. P.; Tan, Yee-Joo (2007): Expression, glycosylation, and modification of the spike (S) glycoprotein of SARS CoV. In: Methods in molecular biology (Clifton, N.J.) 379, S. 127–135. DOI: 10.1007/978-1-59745-393-6_9.</ref>
 +
</StructureSection>
-
== See also ==
 
-
[[Coronavirus_Disease 2019 (COVID-19)]]
 
-
__NOTOC__
 
-
</SX>
 
== References ==
== References ==
<references/>
<references/>

Revision as of 05:55, 21 April 2020

Spike Glycoprotein

Cryo-EM reconstruction of the spike. It consists of 3 monomers of the Spike glycoprotein (pdb code 6vsb)

Drag the structure with the mouse to rotate

References

  1. 1.0 1.1 Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola et al. (2020): Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. In: Science 367 (6483), S. 1260–1263. DOI: 10.1126/science.abb2507.
  2. 2.0 2.1 Lan, Jun; Ge, Jiwan; Yu, Jinfang; Shan, Sisi; Zhou, Huan; Fan, Shilong et al. (2020): Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. In: Nature. DOI: 10.1038/s41586-020-2180-5.
  3. Yan, Renhong; Zhang, Yuanyuan; Li, Yaning; Xia, Lu; Guo, Yingying; Zhou, Qiang (2020): Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. In: Science 367 (6485), S. 1444–1448. DOI: 10.1126/science.abb2762.
  4. Xia, Shuai; Zhu, Yun; Liu, Meiqin; Lan, Qiaoshuai; Xu, Wei; Wu, Yanling et al. (2020): Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. In: Cellular & molecular immunology. DOI: 10.1038/s41423-020-0374-2.
  5. Walls, Alexandra C.; Park, Young-Jun; Tortorici, M. Alejandra; Wall, Abigail; McGuire, Andrew T.; Veesler, David (2020): Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. In: Cell. DOI: 10.1016/j.cell.2020.02.058.
  6. Shen, Shuo; Tan, Timothy H. P.; Tan, Yee-Joo (2007): Expression, glycosylation, and modification of the spike (S) glycoprotein of SARS CoV. In: Methods in molecular biology (Clifton, N.J.) 379, S. 127–135. DOI: 10.1007/978-1-59745-393-6_9.
Personal tools