2d31

Crystal structure of disulfide-linked HLA-G dimer

spinqualitylabelsall models 2d31, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2d31 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HLAG_HUMAN Involved in the presentation of foreign antigens to the immune system. Plays a role in maternal tolerance of the fetus by mediating protection from the deleterious effects of natural killer cells, cytotoxic T-lymphocytes, macrophages and mononuclear cells. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed HLA-G is a nonclassical major histocompatibility complex class I (MHCI) molecule, which is expressed in trophoblasts and confers immunological tolerance in the maternal-fetal interface by binding to leukocyte Ig-like receptors (LILRs, also called as LIR/ILT/CD85) and CD8. HLA-G is expressed in disulfide-linked dimer form both in solution and at the cell surface. Interestingly, MHCI dimer formations have been involved in pathogenesis and T cell activation. The structure and receptor binding characteristics of MHCI dimers have never been evaluated. Here we performed binding studies showing that the HLA-G dimer exhibited higher overall affinity to LILRB1/2 than the monomer by significant avidity effects. Furthermore, the cell reporter assay demonstrated that the dimer formation remarkably enhanced the LILRB1-mediated signaling at the cellular level. We further determined the crystal structure of the wild-type dimer of HLA-G with the intermolecular Cys(42)-Cys(42) disulfide bond. This dimer structure showed the oblique configuration to expose two LILR/CD8-binding sites upward from the membrane easily accessible for receptors, providing plausible 1:2 (HLA-G dimer:receptors) complex models. These results indicated that the HLA-G dimer conferred increased avidity in a proper structural orientation to induce efficient LILR signaling, resulting in the dominant immunosuppressive effects. Moreover, structural and functional implications for other MHCI dimers observed in activated T cells and the pathogenic allele, HLA-B27, are discussed. Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer.,Shiroishi M, Kuroki K, Ose T, Rasubala L, Shiratori I, Arase H, Tsumoto K, Kumagai I, Kohda D, Maenaka K J Biol Chem. 2006 Apr 14;281(15):10439-47. Epub 2006 Feb 2. PMID:16455647 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures MHC 3D structures MHC I 3D structures

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