7KEC

SARS-CoV-2 D614G 1-RBD-up Spike Protein Trimer without the P986-P987 stabilizing mutations (S-GSAS-D614G Sub-Classification)

7KEC の概要

• エントリーDOI: 10.2210/pdb7kec/pdb
• EMDBエントリー: 22831 22832 22833 22834 22835 22836 22837 22838
• 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: sars-cov-2 spike protein trimer, 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: 439518.94

構造登録者

Gobeil, S.,Acharya, P. (登録日: 2020-10-10, 公開日: 2020-11-04, 最終更新日: 2024-11-20)

主引用文献

Gobeil, S.M.,Janowska, K.,McDowell, S.,Mansouri, K.,Parks, R.,Manne, K.,Stalls, V.,Kopp, M.F.,Henderson, R.,Edwards, R.J.,Haynes, B.F.,Acharya, P.
D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction.
Cell Rep, 34:108630-108630, 2021

PubMed Abstract: The severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein is the target of vaccine design efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Despite a low mutation rate, isolates with the D614G substitution in the S protein appeared early during the pandemic and are now the dominant form worldwide. Here, we explore S conformational changes and the effects of the D614G mutation on a soluble S ectodomain construct. Cryoelectron microscopy (cryo-EM) structures reveal altered receptor binding domain (RBD) disposition; antigenicity and proteolysis experiments reveal structural changes and enhanced furin cleavage efficiency of the G614 variant. Furthermore, furin cleavage alters the up/down ratio of the RBDs in the G614 S ectodomain, demonstrating an allosteric effect on RBD positioning triggered by changes in the SD2 region, which harbors residue 614 and the furin cleavage site. Our results elucidate SARS-CoV-2 S conformational landscape and allostery and have implications for vaccine design.

PubMed: 33417835
DOI: 10.1016/j.celrep.2020.108630

実験手法

ELECTRON MICROSCOPY (3.84 Å)