8VKN

Cryo-EM structure of SARS-CoV-2 XBB.1.5 spike protein in complex with mouse ACE2 (focused refinement of RBD and mouse ACE2)

8VKN の概要

• エントリーDOI: 10.2210/pdb8vkn/pdb
• EMDBエントリー: 43323
• 分子名称: Spike protein S1, Angiotensin-converting enzyme 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: complex, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 95608.20

構造登録者

Zhu, X.,Mannar, D.,Saville, J.,Poloni, C.,Bezeruk, A.,Tidey, K.,Ahmed, S.,Tuttle, K.,Vahdatihassani, F.,Cholak, S.,Cook, L.,Steiner, T.S.,Subramaniam, S. (登録日: 2024-01-09, 公開日: 2024-02-14, 最終更新日: 2025-02-26)

主引用文献

Mannar, D.,Saville, J.W.,Poloni, C.,Zhu, X.,Bezeruk, A.,Tidey, K.,Ahmed, S.,Tuttle, K.S.,Vahdatihassani, F.,Cholak, S.,Cook, L.,Steiner, T.S.,Subramaniam, S.
Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein.
Nat Commun, 15:1854-1854, 2024

PubMed Abstract: The XBB.1.5 variant of SARS-CoV-2 has rapidly achieved global dominance and exhibits a high growth advantage over previous variants. Preliminary reports suggest that the success of XBB.1.5 stems from mutations within its spike glycoprotein, causing immune evasion and enhanced receptor binding. We present receptor binding studies that demonstrate retention of binding contacts with the human ACE2 receptor and a striking decrease in binding to mouse ACE2 due to the revertant R493Q mutation. Despite extensive evasion of antibody binding, we highlight a region on the XBB.1.5 spike protein receptor binding domain (RBD) that is recognized by serum antibodies from a donor with hybrid immunity, collected prior to the emergence of the XBB.1.5 variant. T cell assays reveal high frequencies of XBB.1.5 spike-specific CD4 and CD8 T cells amongst donors with hybrid immunity, with the CD4 T cells skewed towards a Th1 cell phenotype and having attenuated effector cytokine secretion as compared to ancestral spike protein-specific cells. Thus, while the XBB.1.5 variant has retained efficient human receptor binding and gained antigenic alterations, it remains susceptible to recognition by T cells induced via vaccination and previous infection.

PubMed: 38424106
DOI: 10.1038/s41467-024-46104-2

実験手法

ELECTRON MICROSCOPY (2.93 Å)