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You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue.
Structural highlights
6vsb is a homotrimer transmembrane glycoprotein(S) protruding from the viral surface¹. It is composed by two subunits that are fundamental for the virus entry in the cell: The S1 subunit, a v shaped subunit which contains the receptor binding domain (RBD), is responsible for binding to the host cell receptor, and the S2 subunit, responsible for fusion of the viral and cellular membranes. In order to allow the binding of the RBD in S1 with the host cell, the spike protein goes through conformational changes that make the binding domain assume a up conformation, thus, exposing the spike protein to its target receptor.
This protein also shares amino acid sequence identity of 76% with SARS-CoV, however, as shown in the figure bellow, it has inserted amino acids that indicate a furin like cleavage site in the S1/S2 boundary. that must be primed in order to enable the viral pathogenicity. Regarding its secundary structure, units of beta-sheets, alpha-helices and loops can be observed thoughout the protein.
Figure 1: Alignment of S in between multiple SARS-CoV (Walls et al., 2020)
Function
The spike glycoprotein binds the viral structure to the hosts cell's angiotensin-converting enzime 2 (1r42). Once bound, it starts the fusion of viral and cellular membrane, therefore enabling the pathogenicity and spread of the virus.
Disease
6vsb is probably the protein that enabled the Sars-Cov-2 to enter human cells, rusulting therefore on the large scale coronavirus epidemics in 2020.
The main symptoms of the COVID-19 were similar to the ones of common cold: fever, cough and tiredness, but with some stronger than the common cold: Chest pain, lost of smell and taste sense.
The main reason for the worst symptoms is the death of several types of cells in the lungs, causing severe loss of oxygenation, therefore, resulting of gradual colapse of the respiratory system of the infected.
Relevance
Due to its role in the infection process, the spike glyprotein may be a potential target of studies that seek methods of preventing COVID-19. These include the development of vaccines based on antibodies that are able to block protein's structure of the protein and on it's recognition/biding mechanisms. For instance, avoiding the cleavage of the furin, located on the B domain of the protein, by the host's proteases could be a way of viral inhibition. Comprehending how the protein can be bound to antibodies could also help the scientific community to prepare for future SARS coronavirus outbreaks that may happen in the future.
Interaction with angiotensin-converting enzime 2
The interaction between the 2019-nCov and the host cell begins with the recognition of the ACE2, a dimeric protein. Then, the S1 subunit moves, modifying the protein's conformation in way that receptor-binding domain becomes available to connect itself to the peptidase domain of the receptor. At that instance, the spike protein is found in a "up" conformation. Due to the existence of four amino acids in between the 680 and 685 positions, a furin cleavage site is featured in the protein. Once this site is cleaved by host's furins, a later cleavage at S2' by a serine protease, TMPRSS2, happens in order to allow the activation of the fusion mechanism. Lastly, the spike protein makes a high affinity bond with ACE2 at the order of 15nM and a complex of spike protein and ACE2, as shown in figure 3, is formed.
Figure 2: Alignment between S protein of SARS and SARS-2 (Hoffmann et al., 2020).
Figure 3: Spike protein and ACE2 bound together (Goodsell, D., 2020)
- ↑ 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:https://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
