8WHV

Spike Trimer of BA.2.86 with three RBDs down

8WHV の概要

• エントリーDOI: 10.2210/pdb8whv/pdb
• EMDBエントリー: 37549
• 分子名称: Spike glycoprotein, beta-D-mannopyranose-(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: surface protein, glycoprotein, spike protein, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 415659.99

構造登録者

Yue, C.,Liu, P. (登録日: 2023-09-23, 公開日: 2024-07-03, 最終更新日: 2024-08-21)

主引用文献

Liu, P.,Yue, C.,Meng, B.,Xiao, T.,Yang, S.,Liu, S.,Jian, F.,Zhu, Q.,Yu, Y.,Ren, Y.,Wang, P.,Li, Y.,Wang, J.,Mao, X.,Shao, F.,Wang, Y.,Gupta, R.K.,Cao, Y.,Wang, X.
Spike N354 glycosylation augments SARS-CoV-2 fitness for human adaptation through structural plasticity.
Natl Sci Rev, 11:nwae206-nwae206, 2024

PubMed Abstract: Selective pressures have given rise to a number of SARS-CoV-2 variants during the prolonged course of the COVID-19 pandemic. Recently evolved variants differ from ancestors in additional glycosylation within the spike protein receptor-binding domain (RBD). Details of how the acquisition of glycosylation impacts viral fitness and human adaptation are not clearly understood. Here, we dissected the role of N354-linked glycosylation, acquired by BA.2.86 sub-lineages, as a RBD conformational control element in attenuating viral infectivity. The reduced infectivity is recovered in the presence of heparin sulfate, which targets the 'N354 pocket' to ease restrictions of conformational transition resulting in a 'RBD-up' state, thereby conferring an adjustable infectivity. Furthermore, N354 glycosylation improved spike cleavage and cell-cell fusion, and in particular escaped one subset of ADCC antibodies. Together with reduced immunogenicity in hybrid immunity background, these indicate a single spike amino acid glycosylation event provides selective advantage in humans through multiple mechanisms.

PubMed: 39071099
DOI: 10.1093/nsr/nwae206

実験手法

ELECTRON MICROSCOPY (3.32 Å)