8RNF

HLA-E*01:03 in complex with SARS-CoV-2 Omicron Nsp13 peptide, VIPLSAPTL

8RNF の概要

• エントリーDOI: 10.2210/pdb8rnf/pdb
• 分子名称: HLA class I histocompatibility antigen, E alpha chain variant, Beta-2-microglobulin, Non-structural protein 7, ... (4 entities in total)
• 機能のキーワード: sars-cov-2, covid-19, hla-e, nk cells, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 133161.53

構造登録者

Sun, R.,Achour, A.,Sala, B.M.,Sandalova, T. (登録日: 2024-01-09, 公開日: 2024-12-04, 最終更新日: 2025-01-22)

主引用文献

Bilev, E.,Wild, N.,Momayyezi, P.,Sala, B.M.,Sun, R.,Sandalova, T.,Marquardt, N.,Ljunggren, H.G.,Achour, A.,Hammer, Q.
Emerging mutation in SARS-CoV-2 facilitates escape from NK cell recognition and associates with enhanced viral fitness.
Plos Pathog., 20:e1012755-e1012755, 2024

PubMed Abstract: In addition to adaptive immunity, natural killer (NK) cells of the innate immune system contribute to the control of viral infections. The HLA-E-restricted SARS-CoV-2 Nsp13232-240 epitope VMPLSAPTL renders infected cells susceptible to NK cells by preventing binding to the inhibitory receptor NKG2A. Here, we report that a recently emerged methionine to isoleucine substitution at position 2 (pM2I) of Nsp13232-240 impairs binding of the mutated epitope to HLA-E and diminishes HLA-E/peptide complex stability. Structural analyses revealed altered occupancy of the HLA-E B-pocket as the underlying cause for reduced presentation and stability of the mutated epitope. Functionally, the reduced presentation of the mutated epitope correlated with elevated binding to NKG2A as well as with increased NK cell inhibition. Moreover, the pM2I mutation associated with enhanced estimated viral fitness and was transmitted to descendants of the SARS-CoV-2 BQ.1 variant. Interestingly, the mutated epitope resembles sequences of related peptides found in endemic common cold-causing human coronaviruses. Altogether, these findings indicate compromised peptide presentation as a viral adaptation to evade NK cell-mediated immunosurveillance by enabling enhanced presentation of self-peptide and restoring NKG2A-dependent inhibition of NK cells.

PubMed: 39652590
DOI: 10.1371/journal.ppat.1012755

実験手法

X-RAY DIFFRACTION (1.872 Å)