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PDBsum entry 2dyp
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Immune system
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PDB id
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2dyp
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Contents |
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275 a.a.
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100 a.a.
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185 a.a.
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References listed in PDB file
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Key reference
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Title
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Structural basis for recognition of the nonclassical mhc molecule hla-G by the leukocyte ig-Like receptor b2 (lilrb2/lir2/ilt4/cd85d).
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Authors
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M.Shiroishi,
K.Kuroki,
L.Rasubala,
K.Tsumoto,
I.Kumagai,
E.Kurimoto,
K.Kato,
D.Kohda,
K.Maenaka.
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Ref.
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Proc Natl Acad Sci U S A, 2006,
103,
16412-16417.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 3.
Fig. 3. LILR binding interfaces (site 2) of the  3 domain
of the LILRB2/HLA-G and LILRB1/HLA-A2 complexes. (A and C)
LILRB2/HLA-G complex. (B and D) LILRB1/HLA-A2 complex. Cyan,
HLA-G heavy chain; light blue, HLA-A2 heavy chain; green and
light green,  [2]m; magenta, LILRB2;
yellow, LILRB1. (A and B) The binding interface around the
195–197 loop of HLA-G. (C and D) The binding interface around
the cleft between the first 3[10] helix and the C strand of
LILRBs.
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Figure 4.
Fig. 4. SPR analyses. Binding of LILRB2 (Left) and LILRB1
(Right) to HLA-G heterotrimer (red lines) and [2]m-free
HLA-G heavy chain (green lines). Heterotrimers and [2]m-free
forms of MHCIs were immobilized on the sensor chip at  2,000
response units (RU). Black lines show the responses to the
control protein (BSA).
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