2d31

From Proteopedia

Crystal structure of disulfide-linked HLA-G dimer

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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