7MTC

Structure of freshly purified SARS-CoV-2 S2P spike at pH 7.4

7MTC の概要

• エントリーDOI: 10.2210/pdb7mtc/pdb
• 関連するPDBエントリー: 7MTD 7MTE
• EMDBエントリー: 23982 23983 23984
• 分子名称: 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)
• 機能のキーワード: covid-19, sars-cov-2 spike, s2p, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 433636.92

構造登録者

Tsybovsky, Y.,Olia, A.S.,Kwong, P.D. (登録日: 2021-05-13, 公開日: 2021-09-15, 最終更新日: 2025-05-14)

主引用文献

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

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: 34461095
DOI: 10.1016/j.jbc.2021.101127

実験手法

ELECTRON MICROSCOPY (2.6 Å)