6CYW

Structure of sphingomyelin in complex with mouse CD1d

6CYW の概要

• エントリーDOI: 10.2210/pdb6cyw/pdb
• 分子名称: Antigen-presenting glycoprotein CD1d1, Beta-2-microglobulin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: glycolipid-antigen presentation, mhc-fold, ig-fold, 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: 45974.07

構造登録者

Zajonc, D.M.,Wang, J. (登録日: 2018-04-06, 公開日: 2019-04-10, 最終更新日: 2024-10-30)

主引用文献

Melum, E.,Jiang, X.,Baker, K.D.,Macedo, M.F.,Fritsch, J.,Dowds, C.M.,Wang, J.,Pharo, A.,Kaser, A.,Tan, C.,Pereira, C.S.,Kelly, S.L.,Duan, J.,Karlsen, T.H.,Exley, M.A.,Schutze, S.,Zajonc, D.M.,Merrill, A.H.,Schuchman, E.H.,Zeissig, S.,Blumberg, R.S.
Control of CD1d-restricted antigen presentation and inflammation by sphingomyelin.
Nat.Immunol., 20:1644-1655, 2019

PubMed Abstract: Invariant natural killer T (iNKT) cells recognize activating self and microbial lipids presented by CD1d. CD1d can also bind non-activating lipids, such as sphingomyelin. We hypothesized that these serve as endogenous regulators and investigated humans and mice deficient in acid sphingomyelinase (ASM), an enzyme that degrades sphingomyelin. We show that ASM absence in mice leads to diminished CD1d-restricted antigen presentation and iNKT cell selection in the thymus, resulting in decreased iNKT cell levels and resistance to iNKT cell-mediated inflammatory conditions. Defective antigen presentation and decreased iNKT cells are also observed in ASM-deficient humans with Niemann-Pick disease, and ASM activity in healthy humans correlates with iNKT cell phenotype. Pharmacological ASM administration facilitates antigen presentation and restores the levels of iNKT cells in ASM-deficient mice. Together, these results demonstrate that control of non-agonistic CD1d-associated lipids is critical for iNKT cell development and function in vivo and represents a tight link between cellular sphingolipid metabolism and immunity.

PubMed: 31636468
DOI: 10.1038/s41590-019-0504-0

実験手法

X-RAY DIFFRACTION (1.95 Å)