2DYP

Crystal Structure of LILRB2(LIR2/ILT4/CD85d) complexed with HLA-G

Summary for 2DYP

• Entry DOI: 10.2210/pdb2dyp/pdb
• Related: 1YPD 2D31 2GW5
• Descriptor: HLA class I histocompatibility antigen, alpha chain G, Beta-2-microglobulin, 9 Mer Peptide From Histone H2A.x, ... (5 entities in total)
• Functional Keywords: immunoglobulin-like, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P17693 Q8N423; Secreted: P61769; Nucleus: P16104
• Total number of polymer chains: 4
• Total formula weight: 66941.96

Authors

Shiroishi, M.,Kuroki, K.,Rasubala, L.,Kohda, D.,Maenaka, K. (deposition date: 2006-09-15, release date: 2006-11-07, Last modification date: 2024-10-16)

Primary citation

Shiroishi, M.,Kuroki, K.,Rasubala, L.,Tsumoto, K.,Kumagai, I.,Kurimoto, E.,Kato, K.,Kohda, D.,Maenaka, K.
Structural basis for recognition of the nonclassical MHC molecule HLA-G by the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d)
Proc.Natl.Acad.Sci.Usa, 103:16412-16417, 2006

PubMed Abstract: HLA-G is a nonclassical MHC class I (MHCI) molecule that can suppress a wide range of immune responses in the maternal-fetal interface. The human inhibitory immune receptors leukocyte Ig-like receptor (LILR) B1 [also called LIR1, Ig-like transcript 2 (ILT2), or CD85j] and LILRB2 (LIR2/ILT4/CD85d) preferentially recognize HLA-G. HLA-G inherently exhibits various forms, including beta(2)-microglobulin (beta(2)m)-free and disulfide-linked dimer forms. Notably, LILRB1 cannot recognize the beta(2)m-free form of HLA-G or HLA-B27, but LILRB2 can recognize the beta(2)m-free form of HLA-B27. To date, the structural basis for HLA-G/LILR recognition remains to be examined. Here, we report the 2.5-A resolution crystal structure of the LILRB2/HLA-G complex. LILRB2 exhibits an overlapping but distinct MHCI recognition mode compared with LILRB1 and dominantly recognizes the hydrophobic site of the HLA-G alpha3 domain. NMR binding studies also confirmed these LILR recognition differences on both conformed (heavy chain/peptide/beta(2)m) and free forms of beta(2)m. Binding studies using beta(2)m-free MHCIs revealed differential beta(2)m-dependent LILR-binding specificities. These results suggest that subtle structural differences between LILRB family members cause the distinct binding specificities to various forms of HLA-G and other MHCIs, which may in turn regulate immune suppression.

PubMed: 17056715
DOI: 10.1073/pnas.0605228103

Experimental method

X-RAY DIFFRACTION (2.5 Å)