8X50

BA.2.86 Spike Trimer with ins483V mutation (1 RBD up)

Summary for 8X50

• Entry DOI: 10.2210/pdb8x50/pdb
• EMDB information: 38057
• Descriptor: 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)
• Functional Keywords: trimer, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 3
• Total formula weight: 415795.22

Authors

Yue, C.,Liu, P. (deposition date: 2023-11-16, release date: 2024-06-26, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.82 Å)