| Structural highlights
6mjj is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.93Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CD1D1_MOUSE Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.[1] [2] [3]
Publication Abstract from PubMed
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, alpha-galactosylceramide (alpha-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 alpha-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 alpha-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 alpha-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 alpha2-helix of CD1d.
4"-O-Alkylated alpha-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic, Biological, and Structural Studies.,Janssens J, Bitra A, Wang J, Decruy T, Venken K, van der Eycken J, Elewaut D, Zajonc DM, van Calenbergh S ChemMedChem. 2019 Jan 8;14(1):147-168. doi: 10.1002/cmdc.201800649. Epub 2018 Dec, 17. PMID:30556652[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jayawardena-Wolf J, Benlagha K, Chiu YH, Mehr R, Bendelac A. CD1d endosomal trafficking is independently regulated by an intrinsic CD1d-encoded tyrosine motif and by the invariant chain. Immunity. 2001 Dec;15(6):897-908. PMID:11754812
- ↑ Zajonc DM, Maricic I, Wu D, Halder R, Roy K, Wong CH, Kumar V, Wilson IA. Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J Exp Med. 2005 Dec 5;202(11):1517-26. Epub 2005 Nov 28. PMID:16314439 doi:10.1084/jem.20051625
- ↑ Zajonc DM, Cantu C 3rd, Mattner J, Zhou D, Savage PB, Bendelac A, Wilson IA, Teyton L. Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor. Nat Immunol. 2005 Aug;6(8):810-8. Epub 2005 Jul 10. PMID:16007091 doi:10.1038/ni1224
- ↑ Janssens J, Bitra A, Wang J, Decruy T, Venken K, van der Eycken J, Elewaut D, Zajonc DM, van Calenbergh S. 4"-O-Alkylated alpha-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic, Biological, and Structural Studies. ChemMedChem. 2019 Jan 8;14(1):147-168. doi: 10.1002/cmdc.201800649. Epub 2018 Dec, 17. PMID:30556652 doi:http://dx.doi.org/10.1002/cmdc.201800649
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