8UMO

Murine CD94-NKG2A receptor in complex with Qa-1b presenting AMAPRTLLL

Summary for 8UMO

• Entry DOI: 10.2210/pdb8umo/pdb
• Descriptor: H-2 class I histocompatibility antigen, D-37 alpha chain, Beta-2-microglobulin, Killer cell lectin-like receptor, subfamily D, member 1, ... (7 entities in total)
• Functional Keywords: inhibitory receptor, mhc-class i, c-type lectin, transmembrane receptor signalling, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 5
• Total formula weight: 72862.19

Authors

MacLachlan, B.J.,Rossjohn, J.,Vivian, J.P. (deposition date: 2023-10-18, release date: 2024-01-17, Last modification date: 2024-10-16)

Primary citation

MacLachlan, B.J.,Sullivan, L.C.,Brooks, A.G.,Rossjohn, J.,Vivian, J.P.
Structure of the murine CD94-NKG2A receptor in complex with Qa-1 b presenting an MHC-I leader peptide.
Febs J., 291:1530-1544, 2024

PubMed Abstract: The heterodimeric natural killer cells antigen CD94 (CD94)-NKG2-A/NKG2-B type II integral membrane protein (NKG2A) receptor family expressed on human and mouse natural killer (NK) cells monitors global major histocompatibility complex (MHC) class I cell surface expression levels through binding to MHC class Ia-derived leader sequence peptides presented by HLA class I histocompatibility antigen, alpha chain E (HLA-E; in humans) or H-2 class I histocompatibility antigen, D-37 (Qa-1; in mice). Although the molecular basis underpinning human CD94-NKG2A recognition of HLA-E is known, the equivalent interaction in the murine setting is not. By determining the high-resolution crystal structure of murine CD94-NKG2A in complex with Qa-1 presenting the Qa-1 determinant modifier peptide (QDM), we resolved the mode of binding. Compared to the human homologue, the murine CD94-NKG2A-Qa-1-QDM displayed alterations in the distribution of interactions across CD94 and NKG2A subunits that coincide with differences in electrostatic complementarity of the ternary complex and the lack of cross-species reactivity. Nevertheless, we show that Qa-1b could be modified through W65R + N73I mutations to mimic HLA-E, facilitating binding with both human and murine CD94-NKG2A. These data underscore human and murine CD94-NKG2A cross-species heterogeneity and provide a foundation for humanising Qa-1b in immune system models.

PubMed: 38158698
DOI: 10.1111/febs.17050

Experimental method

X-RAY DIFFRACTION (2.6 Å)