8UMO

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

8UMO の概要

• エントリーDOI: 10.2210/pdb8umo/pdb
• 分子名称: 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)
• 機能のキーワード: inhibitory receptor, mhc-class i, c-type lectin, transmembrane receptor signalling, immune system
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 72862.19

構造登録者

MacLachlan, B.J.,Rossjohn, J.,Vivian, J.P. (登録日: 2023-10-18, 公開日: 2024-01-17, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.6 Å)