1ugn | pdb_00001ugn
Crystal structure of LIR1.02, one of the alleles of LIR1
Structural highlights
FunctionLIRB1_HUMAN Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C and HLA-G alleles. Receptor for H301/UL18, a human cytomegalovirus class I MHC homolog. Ligand binding results in inhibitory signals and down-regulation of the immune response. Engagement of LILRB1 present on natural killer cells or T-cells by class I MHC molecules protects the target cells from lysis. Interaction with HLA-B or HLA-E leads to inhibition of the signal triggered by FCER1A and inhibits serotonin release. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedLeukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1/LIR1/ILT2) is an inhibitory receptor broadly expressed on leukocytes and recognizes HLA-class I and human cytomegalovirus UL18. LILRB1 is encoded within the leukocyte receptor complex on 19q13.4, previously implicated to be a susceptibility region to systemic lupus erythematosus (SLE). In this study, we screened for polymorphisms of LILRB1 and examined their association with SLE and rheumatoid arthritis (RA). In the 5' portion of LILRB1, three haplotypes containing four non-synonymous substitutions within the ligand-binding domains and two single nucleotide polymorphisms within the promoter region were identified and designated as PE01-03. In the 3' portion, two haplotypes (CY01, 02) containing a non-synonymous substitution of the cytoplasmic region were identified. CY01 and 02 did not co-segregate with PE01-03. Significant association with susceptibility to SLE or RA was not observed; however, among the subjects not carrying RA-associated HLA-DRB1 shared epitope (SE), LILRB1.PE01/01 diplotype was significantly associated with RA (odds ratio 2.05, P = 0.019 and Pc = 0.038). Gross difference was not observed in the crystal structures, thermostabilities and binding affinities to HLA-class I ligands among LILRB1.PE01-03 haplotype products; however, surface expression of LILRB1 was significantly decreased in lymphocytes and monocytes from the carriers of PE01 haplotype. These findings demonstrated that LILRB1 is highly polymorphic and is associated with susceptibility to RA in HLA-DRB1 SE negative subjects, possibly by insufficient inhibitory signaling in leukocytes. In addition, these observations suggested that the polymorphisms of LILR family members may be substantially involved in the diversity of human immune responses. Extensive polymorphisms of LILRB1 (ILT2, LIR1) and their association with HLA-DRB1 shared epitope negative rheumatoid arthritis.,Kuroki K, Tsuchiya N, Shiroishi M, Rasubala L, Yamashita Y, Matsuta K, Fukazawa T, Kusaoi M, Murakami Y, Takiguchi M, Juji T, Hashimoto H, Kohda D, Maenaka K, Tokunaga K Hum Mol Genet. 2005 Aug 15;14(16):2469-80. Epub 2005 Jul 13. PMID:16014635[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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