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Crystal structure of HLA-G: A nonclassical MHC class I molecule expressed at the fetal–maternal interface
- Source :
- Proceedings of the National Academy of Sciences. 102:3360-3365
- Publication Year :
- 2005
- Publisher :
- Proceedings of the National Academy of Sciences, 2005.
-
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-Å 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 α3 domain of HLA-G, a candidate binding site for the LIR-1 and -2 inhibitory receptors, is structurally distinct from the α3 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.
- Subjects :
- Models, Molecular
Protein Conformation
Molecular Sequence Data
Antigen presentation
Crystallography, X-Ray
Major histocompatibility complex
Mice
Protein structure
HLA Antigens
Pregnancy
HLA-G
MHC class I
Animals
Humans
Amino Acid Sequence
Binding site
Receptor
Maternal-Fetal Exchange
Peptide sequence
HLA-G Antigens
Multidisciplinary
Sequence Homology, Amino Acid
biology
Histocompatibility Antigens Class I
Biological Sciences
Cell biology
Biochemistry
biology.protein
Female
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 102
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....7a2939abeb5211d93d8cfe9d71c6e093