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| Article Authors: | Craig S Clements; Lars Kjer-Nielsen; Lyudmila Kostenko; Hilary L Hoare; Michelle A Dunstone; Eric Moses; Katy Freed; Andrew G Brooks; Jamie Rossjohn; James McCluskey |
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| Article Title: | Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface. |
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| Reference ID: | 735 |
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| Abstract: | HLA-G is a nonclassical major histocompatibility complex class I (MHC-I) molecule that is primarily expressed at the fetal-maternal interface, where it is thought to play a role in protecting the fetus from the maternal immune response. HLA-G binds a limited repertoire of peptides and interacts with the inhibitory leukocyte Ig-like receptors LIR-1 and LIR-2 and possibly with certain natural killer cell receptors. To gain further insights into HLA-G function, we determined the 1.9-A structure of a monomeric HLA-G complexed to a natural endogenous peptide ligand from histone H2A (RIIPRHLQL). An extensive network of contacts between the peptide and the antigen-binding cleft reveal a constrained mode of binding reminiscent of the nonclassical HLA-E molecule, thereby providing a structural basis for the limited peptide repertoire of HLA-G. The alpha3 domain of HLA-G, a candidate binding site for the LIR-1 and -2 inhibitory receptors, is structurally distinct from the alpha3 domains of classical MHC-I molecules, providing a rationale for the observed affinity differences for these ligands. The structural data suggest a head-to-tail mode of dimerization, mediated by an intermolecular disulfide bond, that is consistent with the observation of HLA-G dimers on the cell surface. |
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| Affiliations: | Protein Crystallography Unit, Monash Centre for Synchrotron Science, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia. |
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| Date: | 2005 |
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| Reference Type: | Literature |
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| PubMed ID: | 15718280 |
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| Journal: | Proc Natl Acad Sci U S A |
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| Journal Volume: | 102 |
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| Article Pages: | 3360-5 |
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| Journal ISSN: | 1091-6490 |
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| Article Chemical List: | HLA Antigens;HLA-G antigen;Histocompatibility Antigens Class I |
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| Article MeSH List: | Amino Acid Sequence; Animals; Crystallography, X-Ray; Female; HLA Antigens(chemistry; immunology); Histocompatibility Antigens Class I(chemistry; immunology); Humans; Maternal-Fetal Exchange(immunology); Mice; Models, Molecular; Molecular Sequence Data; Pregnancy; Protein Conformation; Sequence Homology, Amino Acid |
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| Curation Last Updated: | 2011-08-23 20:12:15 |
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