6MJ4

Crystal structure of MCD1D/INKTCR TERNARY COMPLEX bound to glycolipid (XXW)

6MJ4 の概要

• エントリーDOI: 10.2210/pdb6mj4/pdb
• 分子名称: T cell receptor alpha variable 11,T cell receptor alpha variable 11,T cell receptor alpha joining 18,Human nkt tcr alpha chain, chimeric protein, N-[(2S,3S,4R)-3,4-dihydroxy-1-{[4-O-(prop-2-en-1-yl)-alpha-D-galactopyranosyl]oxy}octadecan-2-yl]hexacosanamide, Beta-chain,T cell receptor chain,T cell receptor beta constant 2, CHIMERIC PROTEIN, ... (11 entities in total)
• 機能のキーワード: mhc-fold, ig-fold, glycolipid antigen presentation, t cell receptor, 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: 97065.73

構造登録者

Zajonc, D.M.,Bitra, A.,Janssens, J. (登録日: 2018-09-20, 公開日: 2019-01-09, 最終更新日: 2024-10-23)

主引用文献

Janssens, J.,Bitra, A.,Wang, J.,Decruy, T.,Venken, K.,van der Eycken, J.,Elewaut, D.,Zajonc, D.M.,van Calenbergh, S.
4"-O-Alkylated alpha-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic, Biological, and Structural Studies.
ChemMedChem, 14:147-168, 2019

PubMed Abstract: Invariant natural killer T-cells (iNKT) are a glycolipid-responsive subset of T-lymphocytes that fulfill a pivotal role in the immune system. The archetypical synthetic glycolipid, α-galactosylceramide (α-GalCer), whose molecular framework is inspired by a group of amphiphilic natural products, remains the most studied antigen for iNKT-cells. Nonetheless, the potential of α-GalCer as an immunostimulating agent is compromised by the fact that this glycolipid elicits simultaneous secretion of Th1- and Th2-cytokines. This has incited medicinal chemistry efforts to identify analogues that are able to perturb the Th1/Th2 balance. In this work, we present the synthesis of an extensive set of 4"-O-alkylated α-GalCer analogues, which were evaluated in vivo for their cytokine induction. We have found that conversion of the 4"-OH group to ether moieties decreases the immunogenic potential in mice relative to α-GalCer. Yet, the benzyl-modified glycolipids are able to produce a distinct pro-inflammatory immune response. The crystal structures suggest an extra hydrophobic interaction between the benzyl moiety and the α2-helix of CD1d.

PubMed: 30556652
DOI: 10.1002/cmdc.201800649

実験手法

X-RAY DIFFRACTION (2 Å)