6k60

Structural and functional basis for HLA-G isoform recognition of immune checkpoint receptor LILRBs

spinqualitylabelsall models 6k60, resolution 3.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6k60 is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: IOD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation. Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis. Function [HLAG_HUMAN] Involved in the presentation of foreign antigens to the immune system. Plays a role in maternal tolerance of the fetus by mediating protection from the deleterious effects of natural killer cells, cytotoxic T-lymphocytes, macrophages and mononuclear cells. [B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMed Human leukocyte Ig-like receptors (LILR) LILRB1 and LILRB2 are immune checkpoint receptors that regulate a wide range of physiological responses by binding to diverse ligands, including HLA-G. HLA-G is exclusively expressed in the placenta, some immunoregulatory cells, and tumors and has several unique isoforms. However, the recognition of HLA-G isoforms by LILRs is poorly understood. In this study, we characterized LILR binding to the beta2-microglobulin (beta2m)-free HLA-G1 isoform, which is synthesized by placental trophoblast cells and tends to dimerize and multimerize. The multimerized beta2m-free HLA-G1 dimer lacked detectable affinity for LILRB1, but bound strongly to LILRB2. We also determined the crystal structure of the LILRB1 and HLA-G1 complex, which adopted the typical structure of a classical HLA class I complex. LILRB1 exhibits flexible binding modes with the alpha3 domain, but maintains tight contacts with beta2m, thus accounting for beta2m-dependent binding. Notably, both LILRB1 and B2 are oriented at suitable angles to permit efficient signaling upon complex formation with HLA-G1 dimers. These structural and functional features of ligand recognition by LILRs provide novel insights into their important roles in the biological regulations. Structural and Functional Basis for LILRB Immune Checkpoint Receptor Recognition of HLA-G Isoforms.,Kuroki K, Matsubara H, Kanda R, Miyashita N, Shiroishi M, Fukunaga Y, Kamishikiryo J, Fukunaga A, Fukuhara H, Hirose K, Hunt JS, Sugita Y, Kita S, Ose T, Maenaka K J Immunol. 2019 Nov 6. pii: jimmunol.1900562. doi: 10.4049/jimmunol.1900562. PMID:31694909 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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