7A4N

Cryo-EM structure of a prefusion stabilized SARS-CoV-2 Spike (D614N, R682S, R685G, A892P, A942P and V987P)(S-closed trimer)

7A4N の概要

• エントリーDOI: 10.2210/pdb7a4n/pdb
• EMDBエントリー: 11639
• 分子名称: Spike glycoprotein,Fibritin, 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: sars-cov-2, virology, covid-19, class i fusion proteins, s glycoprotein, cryo-em, viral protein, prefusion, corona
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 432233.35

構造登録者

Rutten, L.,Renault, L.L.R.,Juraszek, J.,Langedijk, J.P.M. (登録日: 2020-08-20, 公開日: 2020-11-04, 最終更新日: 2024-10-23)

主引用文献

Juraszek, J.,Rutten, L.,Blokland, S.,Bouchier, P.,Voorzaat, R.,Ritschel, T.,Bakkers, M.J.G.,Renault, L.L.R.,Langedijk, J.P.M.
Stabilizing the closed SARS-CoV-2 spike trimer.
Nat Commun, 12:244-244, 2021

PubMed Abstract: The trimeric spike (S) protein of SARS-CoV-2 is the primary focus of most vaccine design and development efforts. Due to intrinsic instability typical of class I fusion proteins, S tends to prematurely refold to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yields. To support ongoing vaccine development efforts, we report the structure-based design of soluble S trimers with increased yields and stabilities, based on introduction of single point mutations and disulfide-bridges. We identify regions critical for stability: the heptad repeat region 1, the SD1 domain and position 614 in SD2. We combine a minimal selection of mostly interprotomeric mutations to create a stable S-closed variant with a 6.4-fold higher expression than the parental construct while no longer containing a heterologous trimerization domain. The cryo-EM structure reveals a correctly folded, predominantly closed pre-fusion conformation. Highly stable and well producing S protein and the increased understanding of S protein structure will support vaccine development and serological diagnostics.

PubMed: 33431842
DOI: 10.1038/s41467-020-20321-x

実験手法

ELECTRON MICROSCOPY (2.75 Å)