| Structural highlights
3tvm is a 8 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.
| | Ligands: | , , , , |
| Related: | 3rzc, 3t1f, 3ta3 |
| Gene: | Cd1.1, CD1d, Cd1d1 (Mus musculus), beta-2-microglobulin (Mus musculus), Valpha14 (mouse variable domain, human constant domain) (Homo sapiens), Vbeta8.2 (mouse variable domain, human constant domain) (Mus musculus) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
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] [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
Publication Abstract from PubMed
Natural killer T (NKT) cells recognize glycolipids presented by CD1d. The first antigen described, alpha-galactosyl ceramide (alphaGalCer), is a potential anticancer agent whose activity depends upon IFN-gamma secretion. We report two analogs of alphaGalCer based on a naturally occurring glycosphingolipid, plakoside A. These compounds induce enhanced IFN-gamma that correlates with detergent-resistant binding to CD1d and an increased stability of the lipid-CD1d complexes on antigen-presenting cells. Structural analysis on one of the analogs indicates that it is more deeply bound inside the CD1d groove, suggesting tighter lipid-CD1d interactions. To our knowledge, this is the first example in which structural information provides an explanation for the increased lipid-CD1d stability, likely responsible for the Th1 bias. We provide insights into the mechanism of IFN-gamma-inducing compounds, and because our compounds activate human NKT cells, they could have therapeutic utility.
Glycolipids that Elicit IFN-gamma-Biased Responses from Natural Killer T Cells.,Tyznik AJ, Farber E, Girardi E, Birkholz A, Li Y, Chitale S, So R, Arora P, Khurana A, Wang J, Porcelli SA, Zajonc DM, Kronenberg M, Howell AR Chem Biol. 2011 Dec 23;18(12):1620-30. PMID:22195564[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
- ↑ Tyznik AJ, Farber E, Girardi E, Birkholz A, Li Y, Chitale S, So R, Arora P, Khurana A, Wang J, Porcelli SA, Zajonc DM, Kronenberg M, Howell AR. Glycolipids that Elicit IFN-gamma-Biased Responses from Natural Killer T Cells. Chem Biol. 2011 Dec 23;18(12):1620-30. PMID:22195564 doi:10.1016/j.chembiol.2011.10.015
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