2akr

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2akr, resolution 1.90Å

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Structural basis of sulfatide presentation by mouse CD1d

Overview

Sulfatide derived from the myelin stimulates a distinct population of, CD1d-restricted natural killer T (NKT) cells. Cis-tetracosenoyl sulfatide, is one of the immunodominant species in myelin as identified by, proliferation, cytokine secretion, and CD1d tetramer staining. The crystal, structure of mouse CD1d in complex with cis-tetracosenoyl sulfatide at 1.9, A resolution reveals that the longer cis-tetracosenoyl fatty acid chain, fully occupies the A' pocket of the CD1d binding groove, whereas the, sphingosine chain fills up the F' pocket. A precise hydrogen bond network, in the center of the binding groove orients and positions the ceramide, backbone for insertion of the lipid tails in their respective pockets. The, 3'-sulfated galactose headgroup is highly exposed for presentation to the, T cell receptor and projects up and away from the binding pocket due to, its beta linkage, compared with the more intimate binding of the, alpha-glactosyl ceramide headgroup to CD1d. These structure and binding, data on sulfatide presentation by CD1d have important implications for the, design of therapeutics that target T cells reactive for myelin glycolipids, in autoimmune diseases of the central nervous system.

About this Structure

2AKR is a Protein complex structure of sequences from Mus musculus with NAG and CIS as ligands. Full crystallographic information is available from OCA.

Reference

Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity., Zajonc DM, Maricic I, Wu D, Halder R, Roy K, Wong CH, Kumar V, Wilson IA, J Exp Med. 2005 Dec 5;202(11):1517-26. Epub 2005 Nov 28. PMID:16314439

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