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PDBsum entry 2akr
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Immune system
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PDB id
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2akr
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References listed in PDB file
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Key reference
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Title
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Structural basis for cd1d presentation of a sulfatide derived from myelin and its implications for autoimmunity.
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Authors
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D.M.Zajonc,
I.Maricic,
D.Wu,
R.Halder,
K.Roy,
C.H.Wong,
V.Kumar,
I.A.Wilson.
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Ref.
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J Exp Med, 2005,
202,
1517-1526.
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PubMed id
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Abstract
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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.
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