3QUY

Structure of the mouse CD1d-BnNH-GSL-1'-iNKT TCR complex

3QUY の概要

• エントリーDOI: 10.2210/pdb3quy/pdb
• 関連するPDBエントリー: 3QUX 3QUZ
• 分子名称: Antigen-presenting glycoprotein CD1d1, Beta-2 microglobulin, Valpha14 (mouse variable domain, human constant domain), ... (9 entities in total)
• 機能のキーワード: antigen presentation, glycolipid, nkt cells, immune system
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 96442.13

構造登録者

Li, Y.,Girardi, E.,Yu, E.D.,Zajonc, D.M. (登録日: 2011-02-24, 公開日: 2011-06-29, 最終更新日: 2024-10-09)

主引用文献

Aspeslagh, S.,Li, Y.,Yu, E.D.,Pauwels, N.,Trappeniers, M.,Girardi, E.,Decruy, T.,Van Beneden, K.,Venken, K.,Drennan, M.,Leybaert, L.,Wang, J.,Franck, R.W.,Van Calenbergh, S.,Zajonc, D.M.,Elewaut, D.
Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis.
Embo J., 30:2294-2305, 2011

PubMed Abstract: Invariant natural killer T (iNKT) cells are known to have marked immunomodulatory capacity due to their ability to produce copious amounts of effector cytokines. Here, we report the structure and function of a novel class of aromatic α-galactosylceramide structurally related glycolipids with marked Th1 bias in both mice and men, leading to superior tumour protection in vivo. The strength of the Th1 response correlates well with enhanced lipid binding to CD1d as a result of an induced fit mechanism that binds the aromatic substitution as a third anchor, in addition to the two lipid chains. This induced fit is in contrast to another Th1-biasing glycolipid, α-C-GalCer, whose CD1d binding follows a conventional key-lock principle. These findings highlight the previously unexploited flexibility of CD1d in accommodating galactose-modified glycolipids and broaden the range of glycolipids that can stimulate iNKT cells. We speculate that glycolipids can be designed that induce a similar fit, thereby leading to superior and more sustained iNKT cell responses in vivo.

PubMed: 21552205
DOI: 10.1038/emboj.2011.145

実験手法

X-RAY DIFFRACTION (2.25 Å)