7MTD
Structure of aged SARS-CoV-2 S2P spike at pH 7.4
Summary for 7MTD
| Entry DOI | 10.2210/pdb7mtd/pdb |
| Related | 7MTC 7MTE |
| EMDB information | 23982 23983 23984 |
| Descriptor | Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | covid-19, sars-cov-2 spike, s2p, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) |
| Total number of polymer chains | 3 |
| Total formula weight | 433415.71 |
| Authors | Tsybovsky, Y.,Olia, A.S.,Kwong, P.D. (deposition date: 2021-05-13, release date: 2021-09-15, Last modification date: 2025-05-28) |
| Primary citation | Olia, A.S.,Tsybovsky, Y.,Chen, S.J.,Liu, C.,Nazzari, A.F.,Ou, L.,Wang, L.,Kong, W.P.,Leung, K.,Liu, T.,Stephens, T.,Teng, I.T.,Wang, S.,Yang, E.S.,Zhang, B.,Zhang, Y.,Zhou, T.,Mascola, J.R.,Kwong, P.D. SARS-CoV-2 S2P spike ages through distinct states with altered immunogenicity. J.Biol.Chem., 297:101127-101127, 2021 Cited by PubMed Abstract: The SARS-CoV-2 spike is the primary target of virus-neutralizing antibodies and critical to the development of effective vaccines against COVID-19. Here, we demonstrate that the prefusion-stabilized two-proline "S2P" spike-widely employed for laboratory work and clinical studies-unfolds when stored at 4 °C, physiological pH, as observed by electron microscopy (EM) and differential scanning calorimetry, but that its trimeric, native-like conformation can be reacquired by low pH treatment. When stored for approximately 1 week, this unfolding does not significantly alter antigenic characteristics; however, longer storage diminishes antibody binding, and month-old spike elicits virtually no neutralization in mice despite inducing high ELISA-binding titers. Cryo-EM structures reveal the folded fraction of spike to decrease with aging; however, its structure remains largely similar, although with varying mobility of the receptor-binding domain. Thus, the SARS-CoV-2 spike is susceptible to unfolding, which affects immunogenicity, highlighting the need to monitor its integrity. PubMed: 34461095DOI: 10.1016/j.jbc.2021.101127 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
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