8U1G
Prefusion-stabilized SARS-CoV-2 S2 subunit
Summary for 8U1G
| Entry DOI | 10.2210/pdb8u1g/pdb |
| Descriptor | Spike protein S2, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total) |
| Functional Keywords | sars-cov-2 spike, s2-only antigen, prefusion-stabilized stem, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2, COVID-19 virus) |
| Total number of polymer chains | 2 |
| Total formula weight | 116841.30 |
| Authors | Hsieh, C.-L.,McLellan, J.S. (deposition date: 2023-08-31, release date: 2024-01-24, Last modification date: 2024-11-20) |
| Primary citation | Hsieh, C.L.,Leist, S.R.,Miller, E.H.,Zhou, L.,Powers, J.M.,Tse, A.L.,Wang, A.,West, A.,Zweigart, M.R.,Schisler, J.C.,Jangra, R.K.,Chandran, K.,Baric, R.S.,McLellan, J.S. Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge. Nat Commun, 15:1553-1553, 2024 Cited by PubMed Abstract: Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the need to reformulate COVID-19 vaccines. Here, we rationally engineer the sequence-conserved S2 subunit of the SARS-CoV-2 spike protein and characterize the resulting S2-only antigens. Structural studies demonstrate that the introduction of interprotomer disulfide bonds can lock S2 in prefusion trimers, although the apex samples a continuum of conformations between open and closed states. Immunization with prefusion-stabilized S2 constructs elicits broadly neutralizing responses against several sarbecoviruses and protects female BALB/c mice from mouse-adapted SARS-CoV-2 lethal challenge and partially protects female BALB/c mice from mouse-adapted SARS-CoV lethal challenge. These engineering and immunogenicity results should inform the development of next-generation pan-coronavirus therapeutics and vaccines. PubMed: 38378768DOI: 10.1038/s41467-024-45404-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.2 Å) |
Structure validation
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