3VWJ

Ternary crystal structure of the human NKT TCR-CD1d-C20:2 complex

3VWJ の概要

• エントリーDOI: 10.2210/pdb3vwj/pdb
• 関連するPDBエントリー: 2PO6 3HUJ 3VWK
• 分子名称: Antigen-presenting glycoprotein CD1d, Beta-2-microglobulin, NKT15 T cell receptor alpha-chain, ... (8 entities in total)
• 機能のキーワード: cd1d, nkt t cell receptor, alpha-galactosylceramide, protein receptor complex, cell membrane, disulfide bond, endosome, glycoprotein, host-virus interaction, immune response, immunoglobulin domain, innate immunity, lysosome, membrane, transmembrane, disease mutation, glycation, mhc i, pyrrolidone carboxylic acid, secreted, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 96570.24

構造登録者

Wun, K.S.,Rossjohn, J. (登録日: 2012-08-24, 公開日: 2012-10-03, 最終更新日: 2024-10-16)

主引用文献

Wun, K.S.,Ross, F.,Patel, O.,Besra, G.S.,Porcelli, S.A.,Richardson, S.K.,Keshipeddy, S.,Howell, A.R.,Godfrey, D.I.,Rossjohn, J.
Human and mouse type I natural killer T cell antigen receptors exhibit different fine specificities for CD1d-antigen complex
J.Biol.Chem., 287:39139-39148, 2012

PubMed Abstract: Human and mouse type I natural killer T (NKT) cells respond to a variety of CD1d-restricted glycolipid antigens (Ags), with their NKT cell antigen receptors (NKT TCRs) exhibiting reciprocal cross-species reactivity that is underpinned by a conserved NKT TCR-CD1d-Ag docking mode. Within this common docking footprint, the NKT TCR recognizes, to varying degrees of affinity, a range of Ags. Presently, it is unclear whether the human NKT TCRs will mirror the generalities underpinning the fine specificity of the mouse NKT TCR-CD1d-Ag interaction. Here, we assessed human NKT TCR recognition against altered glycolipid ligands of α-galactosylceramide (α-GalCer) and have determined the structures of a human NKT TCR in complex with CD1d-4',4″-deoxy-α-GalCer and CD1d-α-GalCer with a shorter, di-unsaturated acyl chain (C20:2). Altered glycolipid ligands with acyl chain modifications did not affect the affinity of the human NKT TCR-CD1d-Ag interaction. Surprisingly, human NKT TCR recognition is more tolerant to modifications at the 4'-OH position in comparison with the 3'-OH position of α-GalCer, which contrasts the fine specificity of the mouse NKT TCR-CD1d-Ag recognition (4'-OH > 3'-OH). The fine specificity differences between human and mouse NKT TCRs was attributable to differing interactions between the respective complementarity-determining region 1α loops and the Ag. Accordingly, germline encoded fine-specificity differences underpin human and mouse type I NKT TCR interactions, which is an important consideration for therapeutic development and NKT cell physiology.

PubMed: 22995911
DOI: 10.1074/jbc.M112.412320

実験手法

X-RAY DIFFRACTION (3.093 Å)