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2d31
From Proteopedia
(New page: 200px<br /> <applet load="2d31" size="450" color="white" frame="true" align="right" spinBox="true" caption="2d31, resolution 3.20Å" /> '''Crystal structure o...) |
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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=" | + | |
caption="2d31, resolution 3.20Å" /> | caption="2d31, resolution 3.20Å" /> | ||
'''Crystal structure of disulfide-linked HLA-G dimer'''<br /> | '''Crystal structure of disulfide-linked HLA-G dimer'''<br /> | ||
==Overview== | ==Overview== | ||
| - | HLA-G is a nonclassical major histocompatibility complex class I (MHCI) | + | 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== | ==Disease== | ||
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==About this Structure== | ==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:// | + | 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== | ==Reference== | ||
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[[Category: mhc class i]] | [[Category: mhc class i]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:54:51 2008'' |
Revision as of 14:54, 21 February 2008
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Crystal structure of disulfide-linked HLA-G dimer
Contents |
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.
Disease
Known diseases associated with this structure: Asthma, susceptibility to OMIM:[142871], Hypoproteinemia, hypercatabolic OMIM:[109700]
About this Structure
2D31 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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