3GML

Structure of mouse CD1d in complex with C6Ph

3GML の概要

• エントリーDOI: 10.2210/pdb3gml/pdb
• 関連するPDBエントリー: 1Z5L 2AKR 2FIK 2Q7Y 3GMM 3GMN 3GMO 3GMP 3GMQ 3GMR
• 分子名称: T-cell surface glycoprotein CD1d1, Beta-2 microglobulin, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• 機能のキーワード: cd1, nkt cell, glycolipid, antigen presentation, cell membrane, disulfide bond, endosome, glycoprotein, immune response, immunoglobulin domain, innate immunity, lysosome, membrane, transmembrane, mhc i, secreted, immune system
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47784.72

構造登録者

Schiefner, A.,Wilson, I.A. (登録日: 2009-03-14, 公開日: 2009-11-10, 最終更新日: 2024-11-27)

主引用文献

Schiefner, A.,Fujio, M.,Wu, D.,Wong, C.H.,Wilson, I.A.
Structural evaluation of potent NKT cell agonists: implications for design of novel stimulatory ligands.
J.Mol.Biol., 394:71-82, 2009

PubMed Abstract: Natural killer T (NKT) cells are a subset of T cells that are activated by CD1d-glycolipid complexes through a semi-invariant alphabeta T cell receptor (NKT TCR). Upon activation, NKT cells secrete regulatory cytokines that are implicated in T helper cell responses. alpha-Galactosylceramide (alpha-GalCer) is a potent NKT cell agonist when presented by CD1d. Phenyl ring substitutions of the alpha-GalCer fatty acid moiety were recently found to be superior in eliciting regulatory cytokines. Crystal structures of four new mouse CD1d-lipid complexes (five structures), a new PBS-25 complex, and CD1d with an endogenous ligand, at 1.6-1.9 A resolution, reveal that the alpha-GalCer phenyl analogues impart minor structural differences to the A'-pocket, while the sphingosine and galactose moieties, important for NKT TCR recognition, remain virtually unchanged. The observed differences in cytokine-release profiles appear to be associated with increased stability of the CD1d-glycolipid complexes rather than increased affinity for the NKT TCR. Furthermore, comparison of mouse CD1d-glycolipid complexes in different crystallographic space groups reveals considerable conformational variation, particularly above the F'-pocket, the primary site of interaction with the NKT TCR. We propose that modifications of the sphingosine moiety or other substitutions that decrease alpha-GalCer flexibility would stabilize the F'-pocket. Such compounds might then increase CD1d affinity for the NKT TCR and further enhance the stimulatory and regulatory properties of alpha-GalCer derivatives.

PubMed: 19732779
DOI: 10.1016/j.jmb.2009.08.061

実験手法

X-RAY DIFFRACTION (1.7 Å)