2d31: Difference between revisions

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[[Image:2d31.gif|left|200px]]<br />

[[Image:2d31.gif|left|200px]]<br /><applet load="2d31" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="2d31" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="2d31, resolution 3.20Å" />

'''Crystal structure of disulfide-linked HLA-G dimer'''<br />

==Overview==

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.

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.

==Disease==

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==About this Structure==

2D31 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2D31 OCA].

2D31 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D31 OCA].

==Reference==

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[[Category: mhc class i]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12~~ 21:25:~~45 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:54:51 2008''

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@@ Line 1: / Line 1: @@
-[[Image:2d31.gif|left|200px]]<br />
+[[Image:2d31.gif|left|200px]]<br /><applet load="2d31" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="2d31" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="2d31, resolution 3.20&Aring;" />
 '''Crystal structure of disulfide-linked HLA-G dimer'''<br />
 ==Overview==
-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.
+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.
 ==Disease==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-D31 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2D31 OCA].
+D31 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D31 OCA].
 ==Reference==
@@ Line 29: / Line 28: @@
 [[Category: mhc class i]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:25:45 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:54:51 2008''