8RNF

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

Summary for 8RNF

• Entry DOI: 10.2210/pdb8rnf/pdb
• Descriptor: HLA class I histocompatibility antigen, E alpha chain variant, Beta-2-microglobulin, Non-structural protein 7, ... (4 entities in total)
• Functional Keywords: sars-cov-2, covid-19, hla-e, nk cells, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 133161.53

Authors

Sun, R.,Achour, A.,Sala, B.M.,Sandalova, T. (deposition date: 2024-01-09, release date: 2024-12-04, Last modification date: 2025-01-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.872 Å)