SSF143587

SARS receptor-binding domain-like

SUPERFAMILY entry
Member databaseSUPERFAMILY
SUPERFAMILY typehomologous superfamily

Description
Imported from IPR036326

The CoV Spike (S) protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesised as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). Most CoVs, including SARS-CoV-2, SARS-CoV, and MERS-CoV use the C-domain to bind their receptors. However, CoV such as mouse hepatitis virus (MHV) uses the NTD to bind its receptor, mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a). The S1 NTD contributes to the Spike trimer interface
[2, 3, 1, 4]
.

This superfamily represents the receptor-binding domain (RBD) of the Spike S1 subunit, which binds to angiotensin-converting enzyme 2 (ACE2) in respiratory syndrome coronavirus (SARS-CoV)
[6, 9, 7]
, but not in some bat-derived coronaviruses (BatCoV)
[8, 9]
.

This domain is composed of a core and an external subdomain. During evolution, the core subdomain is structurally preserved, whereas the external subdomain folds into variant structures to engage different receptors. The most conserved part lies in the core-centre sheet that is composed of five antiparallel strands and functions as the scaffold of the core subdomain. Additional conserved elements include the core-centre helices and core-peripheral structures. Characteristic cysteine residues form three disulfide bonds in the core subdomain, further stabilizing the core structure from the interior
[5]
.

The structure of this domain has three layers (α/β/α) with an antiparallel β-sheet of 5 strands.

References
Imported from IPR036326

1.Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry. Shang J, Wan Y, Liu C, Yount B, Gully K, Yang Y, Auerbach A, Peng G, Baric R, Li F. PLoS Pathog. 16, e1008392, (2020). PMID: 32150576

2.Structure, Function, and Evolution of Coronavirus Spike Proteins. Li F. Annu Rev Virol 3, 237-261, (2016). PMID: 27578435

3.Longitudinal Surveillance of Betacoronaviruses in Fruit Bats in Yunnan Province, China During 2009-2016. Luo Y, Li B, Jiang RD, Hu BJ, Luo DS, Zhu GJ, Hu B, Liu HZ, Zhang YZ, Yang XL, Shi ZL. Virol Sin 33, 87-95, (2018). PMID: 29500692

4.Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, Zhou Y, Du L. Cell Mol Immunol 17, 613-620, (2020). PMID: 32203189

5.Identification of the Receptor-Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1. Qian Z, Ou X, Goes LG, Osborne C, Castano A, Holmes KV, Dominguez SR. J. Virol. 89, 8816-27, (2015). View articlePMID: 26085157

6.Structure of severe acute respiratory syndrome coronavirus receptor-binding domain complexed with neutralizing antibody. Prabakaran P, Gan J, Feng Y, Zhu Z, Choudhry V, Xiao X, Ji X, Dimitrov DS. J. Biol. Chem. 281, 15829-36, (2006). View articlePMID: 16597622

7.Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, Zhang Q, Shi X, Wang Q, Zhang L, Wang X. Nature 581, 215-220, (2020). PMID: 32225176

8.Putative Receptor Binding Domain of Bat-Derived Coronavirus HKU9 Spike Protein: Evolution of Betacoronavirus Receptor Binding Motifs. Huang C, Qi J, Lu G, Wang Q, Yuan Y, Wu Y, Zhang Y, Yan J, Gao GF. Biochemistry 55, 5977-5988, (2016). PMID: 27696819

9.Structural basis of receptor recognition by SARS-CoV-2. Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, Geng Q, Auerbach A, Li F. Nature 581, 221-224, (2020). PMID: 32225175

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.