3rzc

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Structure of the self-antigen iGb3 bound to mouse CD1d and in complex with the iNKT TCR

Structural highlights

3rzc 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 2.8Å
Ligands:FUL, LGN, MAN, 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

Invariant NKT (iNKT) cells expressing a semi-invariant Valpha14 TCR recognize self and foreign lipid Ags when presented by the nonclassical MHCI homolog CD1d. Whereas the majority of known iNKT cell Ags are characterized by the presence of a single alpha-linked sugar, mammalian self Ags are beta-linked glycosphingolipids, posing the interesting question of how the semi-invariant TCR can bind to such structurally distinct ligands. In this study, we show that the mouse iNKT TCR recognizes the complex beta-linked Ag isoglobotrihexosylceramide (iGb3; Galalpha1-3-Galbeta1-4-Glcbeta1-1Cer) by forcing the proximal beta-linked sugar of the trisaccharide head group to adopt the typical binding orientation of alpha-linked glycolipids. The squashed iGb3 orientation is stabilized by several interactions between the trisaccharide and CD1d residues. Finally, the formation of novel contacts between the proximal and second sugar of iGb3 and CDR2alpha residues of the TCR suggests an expanded recognition logic that can possibly distinguish foreign Ags from self Ags.

Cutting Edge: Structural Basis for the Recognition of {beta}-Linked Glycolipid Antigens by Invariant NKT Cells.,Yu ED, Girardi E, Wang J, Zajonc DM J Immunol. 2011 Sep 1;187(5):2079-83. Epub 2011 Aug 1. PMID:21810611[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. Yu ED, Girardi E, Wang J, Zajonc DM. Cutting Edge: Structural Basis for the Recognition of {beta}-Linked Glycolipid Antigens by Invariant NKT Cells. J Immunol. 2011 Sep 1;187(5):2079-83. Epub 2011 Aug 1. PMID:21810611 doi:10.4049/jimmunol.1101636

Contents


PDB ID 3rzc

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