4Y16

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

Summary for 4Y16

• Entry DOI: 10.2210/pdb4y16/pdb
• Related: 4Y2D 4Y4F 4Y4H 4Y4K
• Descriptor: Antigen-presenting glycoprotein CD1d1, Beta-2-microglobulin, Chimeric TCR Valpha14/Jalpha18 chain (mouse variable domain, human constant domain), ... (9 entities in total)
• Functional Keywords: mhc-fold, ig-fold, glycolipid antigen presentation, t cell receptor, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 4
• Total formula weight: 96619.29

Authors

Zajonc, D.M.,Nemcovic, M. (deposition date: 2015-02-06, release date: 2015-06-03, Last modification date: 2023-09-27)

Primary citation

Birkholz, A.,Nemcovic, M.,Yu, E.D.,Girardi, E.,Wang, J.,Khurana, A.,Pauwels, N.,Farber, E.,Chitale, S.,Franck, R.W.,Tsuji, M.,Howell, A.,Van Calenbergh, S.,Kronenberg, M.,Zajonc, D.M.
Lipid and Carbohydrate Modifications of alpha-Galactosylceramide Differently Influence Mouse and Human Type I Natural Killer T Cell Activation.
J.Biol.Chem., 290:17206-17217, 2015

PubMed Abstract: The ability of different glycosphingolipids (GSLs) to activate type I natural killer T cells (NKT cells) has been known for 2 decades. The possible therapeutic use of these GSLs has been studied in many ways; however, studies are needed in which the efficacy of promising GSLs is compared under identical conditions. Here, we compare five unique GSLs structurally derived from α-galactosylceramide. 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. Although all glycolipids are bound by the T cell receptor 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.

PubMed: 26018083
DOI: 10.1074/jbc.M115.654814

Experimental method

X-RAY DIFFRACTION (2.6 Å)