4y16

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Crystal structure of the mCD1d/NC-aGC/iNKTCR ternary complex

Structural highlights

4y16 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 2.6Å
Ligands:48G, FUL, NAG
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

The ability of different glycosphingolipids (GSLs) to activate Type I Natural Killer T cells (iNKT cells) has been known for two decades. The possible therapeutic use of these GSLs has been studied in many ways, however studies in which the efficacy of promising GSLs is compared under identical conditions are missing. Here we compare five unique GSLs structurally derived from alpha-galactosylceramide (alphaGalCer). We employed biophysical and biological assays, as well as X-ray crystallography to study the impact of the chemical modifications of the antigen on Type I NKT cell activation. While all glycolipids are bound by the TCR of Type I NKT cells in real-time binding assays with high affinity, only a few activate Type I NKT cells in in vivo or in vitro experiments. The differences in biological responses are likely a result of different pharmacokinetic properties of each lipid, which carry modifications at different parts of the molecule. Our results indicate a need to perform a variety of assays to ascertain the therapeutic potential of Type I NKT cell GSL activators.

Lipid and carbohydrate modifications of alpha-galactosylceramide differently influence mouse and human type I natural killer T cell activation.,Birkholz A, Nemcovic M, Yu ED, Girardi E, Wang J, Khurana A, Pauwels N, Farber E, Chitale S, Franck RW, Tsuji M, Howell A, Van Calenbergh S, Kronenberg M, Zajonc DM J Biol Chem. 2015 May 27. pii: jbc.M115.654814. PMID:26018083[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ Birkholz A, Nemcovic M, Yu ED, Girardi E, Wang J, Khurana A, Pauwels N, Farber E, Chitale S, Franck RW, Tsuji M, Howell A, Van Calenbergh S, Kronenberg M, Zajonc DM. Lipid and carbohydrate modifications of alpha-galactosylceramide differently influence mouse and human type I natural killer T cell activation. J Biol Chem. 2015 May 27. pii: jbc.M115.654814. PMID:26018083 doi:http://dx.doi.org/10.1074/jbc.M115.654814

Contents


PDB ID 4y16

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