7JWY

Structure of SARS-CoV-2 spike at pH 4.5

7JWY の概要

• エントリーDOI: 10.2210/pdb7jwy/pdb
• 関連するPDBエントリー: 6XLU 6XM0 6XM3 6XM4 6XM5
• EMDBエントリー: 22251 22253 22254 22255 22256 22515
• 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, ... (4 entities in total)
• 機能のキーワード: sars-cov-2 covid19, 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: 436708.65

構造登録者

Zhou, T.,Tsybovsky, Y.,Kwong, P.D. (登録日: 2020-08-26, 公開日: 2020-11-25, 最終更新日: 2021-12-15)

主引用文献

Zhou, T.,Tsybovsky, Y.,Gorman, J.,Rapp, M.,Cerutti, G.,Chuang, G.Y.,Katsamba, P.S.,Sampson, J.M.,Schon, A.,Bimela, J.,Boyington, J.C.,Nazzari, A.,Olia, A.S.,Shi, W.,Sastry, M.,Stephens, T.,Stuckey, J.,Teng, I.T.,Wang, P.,Wang, S.,Zhang, B.,Friesner, R.A.,Ho, D.D.,Mascola, J.R.,Shapiro, L.,Kwong, P.D.
Cryo-EM Structures of SARS-CoV-2 Spike without and with ACE2 Reveal a pH-Dependent Switch to Mediate Endosomal Positioning of Receptor-Binding Domains.
Cell Host Microbe, 28:867-879.e5, 2020

PubMed Abstract: The SARS-CoV-2 spike employs mobile receptor-binding domains (RBDs) to engage the human ACE2 receptor and to facilitate virus entry, which can occur through low-pH-endosomal pathways. To understand how ACE2 binding and low pH affect spike conformation, we determined cryo-electron microscopy structures-at serological and endosomal pH-delineating spike recognition of up to three ACE2 molecules. RBDs freely adopted "up" conformations required for ACE2 interaction, primarily through RBD movement combined with smaller alterations in neighboring domains. In the absence of ACE2, single-RBD-up conformations dominated at pH 5.5, resolving into a solitary all-down conformation at lower pH. Notably, a pH-dependent refolding region (residues 824-858) at the spike-interdomain interface displayed dramatic structural rearrangements and mediated RBD positioning through coordinated movements of the entire trimer apex. These structures provide a foundation for understanding prefusion-spike mechanics governing endosomal entry; we suggest that the low pH all-down conformation potentially facilitates immune evasion from RBD-up binding antibody.

PubMed: 33271067
DOI: 10.1016/j.chom.2020.11.004

実験手法

ELECTRON MICROSCOPY (2.5 Å)