2D31

Crystal structure of disulfide-linked HLA-G dimer

Summary for 2D31

• Entry DOI: 10.2210/pdb2d31/pdb
• Descriptor: HLA class I histocompatibility antigen, alpha chain G, Beta-2-microglobulin, 9-mer peptide from Histone H2A (3 entities in total)
• Functional Keywords: mhc class i, immune system-cell cycle complex, immune system/cell cycle
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 89860.29

Authors

Shiroishi, M.,Kuroki, K.,Ose, T.,Rasubala, L.,Shiratori, I.,Arase, H.,Tsumoto, K.,Kumagai, I.,Kohda, D.,Maenaka, K. (deposition date: 2005-09-23, release date: 2006-03-14, Last modification date: 2023-10-25)

Primary citation

Shiroishi, M.,Kuroki, K.,Ose, T.,Rasubala, L.,Shiratori, I.,Arase, H.,Tsumoto, K.,Kumagai, I.,Kohda, D.,Maenaka, K.
Efficient Leukocyte Ig-like Receptor Signaling and Crystal Structure of Disulfide-linked HLA-G Dimer
J.Biol.Chem., 281:10439-10447, 2006

PubMed Abstract: 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.

PubMed: 16455647
DOI: 10.1074/jbc.M512305200

Experimental method

X-RAY DIFFRACTION (3.2 Å)