Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Feb 14;24(4):3774.
doi: 10.3390/ijms24043774.

Distinct Conformations of SARS-CoV-2 Omicron Spike Protein and Its Interaction with ACE2 and Antibody

Myeongsang Lee  1 , Marian Major  2 , Huixiao Hong  1
Affiliations
Review

Distinct Conformations of SARS-CoV-2 Omicron Spike Protein and Its Interaction with ACE2 and Antibody

Myeongsang Lee et al. Int J Mol Sci. .

Abstract

Since November 2021, Omicron has been the dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant that causes the coronavirus disease 2019 (COVID-19) and has continuously impacted human health. Omicron sublineages are still increasing and cause increased transmission and infection rates. The additional 15 mutations on the receptor binding domain (RBD) of Omicron spike proteins change the protein conformation, enabling the Omicron variant to evade neutralizing antibodies. For this reason, many efforts have been made to design new antigenic variants to induce effective antibodies in SARS-CoV-2 vaccine development. However, understanding the different states of Omicron spike proteins with and without external molecules has not yet been addressed. In this review, we analyze the structures of the spike protein in the presence and absence of angiotensin-converting enzyme 2 (ACE2) and antibodies. Compared to previously determined structures for the wildtype spike protein and other variants such as alpha, beta, delta, and gamma, the Omicron spike protein adopts a partially open form. The open-form spike protein with one RBD up is dominant, followed by the open-form spike protein with two RBD up, and the closed-form spike protein with the RBD down. It is suggested that the competition between antibodies and ACE2 induces interactions between adjacent RBDs of the spike protein, which lead to a partially open form of the Omicron spike protein. The comprehensive structural information of Omicron spike proteins could be helpful for the efficient design of vaccines against the Omicron variant.

Keywords: Omicron; SARS-CoV-2; angiotensin-converting enzyme 2; antibody; open-form spike protein; receptor binding domain.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Comparison of RBD sequences (A) and ACE2-bound complex structures (B) of spike proteins of wild type and VOCs. Sequences are obtained from Yin et al. [16], and the sequence alignment was performed using ClustalW. The mutations in RBD are color coded in red. The human ACE2 are plotted in blue. Green and orange colors represent the chains with RBD in up and down conformations, respectively. The structures plotted in this figure were characterized by EM at the highest resolution and were obtained from PDB (7WPA for Omicron, 7VXD for Beta, 7TEX for Delta, and 7V81 for Gamma).
Figure 2
Figure 2
Distinct conformations of Omicron spike protein with ACE2. The conformations (A–C) are BA.1 Omicron spike protein complexed with ACE2. The conformations (D,E) are BA.2 Omicron spike protein complexed with ACE2. The spike protein chain with RBD down conformation is marked in orange and the spike protein chain with RBD up conformation is presented in green. ACE2 is colored in blue.
Figure 3
Figure 3
Distinct conformations of the Omicron spike protein complexed with antibodies. The Omicron spike protein with one RBD in up conformation bound with one XGv347 antibody molecule, another RBD in down conformation bound with one XGv347 antibody molecule (A), two RBDs in up conformations bound with two XGv347 antibody molecules (B), and with all three RBDs in down conformation bound with three XGv347 antibody molecules (C). The spike protein with RBD in the up conformation is presented in cyan and the spike protein with RBD in the down conformation is shown in brown.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Han Y., Yang H. The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID-19): A Chinese perspective. J. Med. Virol. 2020;92:639–644. doi: 10.1002/jmv.25749. - DOI - PMC - PubMed
    1. Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., Wang W., Song H., Huang B., Zhu N., et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet. 2020;395:565–574. doi: 10.1016/S0140-6736(20)30251-8. - DOI - PMC - PubMed
    1. Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W., Tian J.-H., Pei Y.-Y., et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579:265–269. doi: 10.1038/s41586-020-2008-3. - DOI - PMC - PubMed
    1. Zhou H., Yang J., Zhou C., Chen B., Fang H., Chen S., Zhang X., Wang L., Zhang L. A Review of SARS-CoV2: Compared With SARS-CoV and MERS-CoV. Front. Med. 2021;8:628370. doi: 10.3389/fmed.2021.628370. - DOI - PMC - PubMed
    1. Huang Y., Yang C., Xu X.F., Xu W., Liu S.W. Structural and functional properties of SARS-CoV-2 spike protein: Potential antivirus drug development for COVID-19. Acta Pharmacol. Sin. 2020;41:1141–1149. doi: 10.1038/s41401-020-0485-4. - DOI - PMC - PubMed

MeSH terms

Substances

Supplementary concepts

Grants and funding

This work was supported by the internal US FDA Chief Scientist Challenge grant.