D
IPR032500

Spike glycoprotein S1, N-terminal domain, betacoronavirus-like

InterPro entry
Short namebCoV_S1_N
Overlapping
homologous
superfamilies
 
domain relationships

Description

This entry represents the N-terminal domain of the betacoronavirus-like trimeric spike glycoprotein. The distal S1 subunit of the coronavirus spike protein is responsible for receptor binding. S1 contains two domains; an N-terminal galectin-like domain (NTD) and a receptor-binding domain (S1 RBD) also referred to as the S1 CTD or domain B. Either the S1 NTD or S1 RBD, or occasionally both, are involved in binding the host receptors. S1 NTD is located on the side of the spike trimer and mainly recognises sugar receptors
[1, 2, 4, 5]
. For many betacoronaviruses (bCoVs), for example mouse hepatitis virus (MHV), the RBD is located in the NTD. The structure of the MHV S1 NTD showed the same fold as human galectins (galactose-binding lectin), however it does not bind any sugar; instead, it binds to the carcinoembryonic antigen cell-adhesion molecule (CEACAM1) through protein-protein interactions
[2]
. All three CEACAM21a-binding sites in MHV spikes can be fully occupied by CEACAM1a. It has been shown that CEACAM1a binding to the MHV spike weakens the interactions between S1 and S2 and facilitates the proteolysis of the spike protein and dissociation of S1
[2]
. The homologous bovine CoV (BCov) S1 NTD also possesses a galectin fold but binds to sialic acid-containing moieties on host cell membranes, as does the NTD of three other group A b-Covs, namely human CoV (HCoV) OC43, avian b-CoV, and infectious bronchitis virus (IBV)
[3]
. Despite the S1 NTD of human respiratory b-CoV HKU1 being highly homologous to the NTDs of MHV and bovine CoV, it does not bind to either sugar or human CEACAMs and the RBD is found instead in the S1 RBD domain
[3]
.

The bCoV NTDs contain a conserved β-sandwich core, but exhibit variant folds in the peripheral elements located in the top-ceiling region and on the lateral side. The core sandwich comprises in total sixteen anti-parallel β-strands, assembling into three (upper, middle, and lower) β-sheet layers. While showing different compositions and structures, the peripheral elements are topologically equivalent β-sandwich-core insertions, highlighting a divergent evolution process for bCoVs to form different lineages
[4]
.

References

1.Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1. Ou X, Guan H, Qin B, Mu Z, Wojdyla JA, Wang M, Dominguez SR, Qian Z, Cui S. Nat Commun 8, 15216, (2017). PMID: 28534504

2.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

3.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

4.Crystal structure of the S1 subunit N-terminal domain from DcCoV UAE-HKU23 spike protein. Cheng Y, He B, Yang J, Ye F, Lin S, Yang F, Chen Z, Chen Z, Cao Y, Lu G. Virology 535, 74-82, (2019). PMID: 31279241

5.Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD. Wang N, Rosen O, Wang L, Turner HL, Stevens LJ, Corbett KS, Bowman CA, Pallesen J, Shi W, Zhang Y, Leung K, Kirchdoerfer RN, Becker MM, Denison MR, Chappell JD, Ward AB, Graham BS, McLellan JS. Cell Rep 28, 3395-3405.e6, (2019). PMID: 31553909

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