1UGN

Crystal structure of LIR1.02, one of the alleles of LIR1

Summary for 1UGN

• Entry DOI: 10.2210/pdb1ugn/pdb
• Related: 1G0X 1UFU
• Descriptor: Leukocyte immunoglobulin-like receptor 1 (2 entities in total)
• Functional Keywords: immunoglobulin-like folds, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane ; Single-pass type I membrane protein . Isoform 5: Secreted : Q8NHL6
• Total number of polymer chains: 1
• Total formula weight: 22085.72

Authors

Shiroishi, M.,Rasubala, L.,Kuroki, K.,Amano, K.,Tsuchiya, N.,Tokunaga, K.,Kohda, D.,Maenaka, K. (deposition date: 2003-06-17, release date: 2004-08-10, Last modification date: 2024-11-06)

Primary citation

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.
Extensive polymorphisms of LILRB1 (ILT2, LIR1) and their association with HLA-DRB1 shared epitope negative rheumatoid arthritis.
Hum.Mol.Genet., 14:2469-2480, 2005

PubMed Abstract: Leukocyte 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.

PubMed: 16014635
DOI: 10.1093/hmg/ddi247

Experimental method

X-RAY DIFFRACTION (1.8 Å)