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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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* Residue conservation analysis
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PDB id:
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Immune system
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Title:
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Crystal structure of lilrb2(lir2/ilt4/cd85d) complexed with hla-g
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Structure:
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Hla class i histocompatibility antigen, alpha chain g. Chain: a. Fragment: residues in data base 25-300. Synonym: hla g antigen. Engineered: yes. Mutation: yes. Beta-2-microglobulin. Chain: b. Fragment: residues in data base 24-219.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this peptide was chemically synthesized.
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Biol. unit:
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Tetramer (from
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Resolution:
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2.50Å
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R-factor:
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0.233
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R-free:
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0.278
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Authors:
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M.Shiroishi,K.Kuroki,L.Rasubala,D.Kohda,K.Maenaka
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Key ref:
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M.Shiroishi
et al.
(2006).
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 U S A,
103,
16412-16417.
PubMed id:
DOI:
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Date:
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15-Sep-06
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Release date:
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07-Nov-06
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PROCHECK
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Headers
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References
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P17693
(HLAG_HUMAN) -
HLA class I histocompatibility antigen, alpha chain G from Homo sapiens
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Seq:
Struc:
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338 a.a.
275 a.a.*
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DOI no:
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Proc Natl Acad Sci U S A
103:16412-16417
(2006)
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PubMed id:
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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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M.Shiroishi,
K.Kuroki,
L.Rasubala,
K.Tsumoto,
I.Kumagai,
E.Kurimoto,
K.Kato,
D.Kohda,
K.Maenaka.
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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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Selected figure(s)
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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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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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E.A.Donadi,
E.C.Castelli,
A.Arnaiz-Villena,
M.Roger,
D.Rey,
and
P.Moreau
(2011).
Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association.
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Cell Mol Life Sci,
68,
369-395.
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E.D.Carosella,
S.Gregori,
N.Rouas-Freiss,
J.LeMaoult,
C.Menier,
and
B.Favier
(2011).
The role of HLA-G in immunity and hematopoiesis.
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Cell Mol Life Sci,
68,
353-368.
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H.J.Pegram,
D.M.Andrews,
M.J.Smyth,
P.K.Darcy,
and
M.H.Kershaw
(2011).
Activating and inhibitory receptors of natural killer cells.
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Immunol Cell Biol,
89,
216-224.
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L.Amiot,
S.Ferrone,
H.Grosse-Wilde,
and
B.Seliger
(2011).
Biology of HLA-G in cancer: a candidate molecule for therapeutic intervention?
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Cell Mol Life Sci,
68,
417-431.
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T.Takai,
A.Nakamura,
and
S.Endo
(2011).
Role of PIR-B in autoimmune glomerulonephritis.
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J Biomed Biotechnol,
2011,
275302.
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N.G.Walpole,
L.Kjer-Nielsen,
L.Kostenko,
J.McCluskey,
A.G.Brooks,
J.Rossjohn,
and
C.S.Clements
(2010).
The structure and stability of the monomorphic HLA-G are influenced by the nature of the bound peptide.
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J Mol Biol,
397,
467-480.
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PDB codes:
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R.Biassoni,
E.Ugolotti,
and
A.De Maria
(2010).
Comparative analysis of NK-cell receptor expression and function across primate species: Perspective on antiviral defenses.
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Self Nonself,
1,
103-113.
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S.V.Guselnikov,
E.S.Reshetnikova,
A.M.Najakshin,
L.V.Mechetina,
J.Robert,
and
A.V.Taranin
(2010).
The amphibians Xenopus laevis and Silurana tropicalis possess a family of activating KIR-related Immunoglobulin-like receptors.
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Dev Comp Immunol,
34,
308-315.
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T.H.Brondijk,
T.de Ruiter,
J.Ballering,
H.Wienk,
R.J.Lebbink,
H.van Ingen,
R.Boelens,
R.W.Farndale,
L.Meyaard,
and
E.G.Huizinga
(2010).
Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI.
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Blood,
115,
1364-1373.
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PDB code:
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C.Li,
B.L.Houser,
M.L.Nicotra,
and
J.L.Strominger
(2009).
HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells.
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Proc Natl Acad Sci U S A,
106,
5767-5772.
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D.Li,
L.Wang,
L.Yu,
E.C.Freundt,
B.Jin,
G.R.Screaton,
and
X.N.Xu
(2009).
Ig-like transcript 4 inhibits lipid antigen presentation through direct CD1d interaction.
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J Immunol,
182,
1033-1040.
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J.Huang,
J.J.Goedert,
E.J.Sundberg,
T.D.Cung,
P.S.Burke,
M.P.Martin,
L.Preiss,
J.Lifson,
M.Lichterfeld,
M.Carrington,
and
X.G.Yu
(2009).
HLA-B*35-Px-mediated acceleration of HIV-1 infection by increased inhibitory immunoregulatory impulses.
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J Exp Med,
206,
2959-2966.
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K.J.Anderson,
and
R.L.Allen
(2009).
Regulation of T-cell immunity by leucocyte immunoglobulin-like receptors: innate immune receptors for self on antigen-presenting cells.
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Immunology,
127,
8.
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K.Pfistershammer,
A.Lawitschka,
C.Klauser,
J.Leitner,
R.Weigl,
M.H.Heemskerk,
W.F.Pickl,
O.Majdic,
G.A.Böhmig,
G.F.Fischer,
H.T.Greinix,
and
P.Steinberger
(2009).
Allogeneic disparities in immunoglobulin-like transcript 5 induce potent antibody responses in hematopoietic stem cell transplant recipients.
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Blood,
114,
2323-2332.
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Y.Chen,
Y.Shi,
H.Cheng,
Y.Q.An,
and
G.F.Gao
(2009).
Structural immunology and crystallography help immunologists see the immune system in action: how T and NK cells touch their ligands.
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IUBMB Life,
61,
579-590.
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C.Y.Tan,
J.F.Ho,
Y.S.Chong,
A.Loganath,
Y.H.Chan,
J.Ravichandran,
C.G.Lee,
and
S.S.Chong
(2008).
Paternal contribution of HLA-G*0106 significantly increases risk for pre-eclampsia in multigravid pregnancies.
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Mol Hum Reprod,
14,
317-324.
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E.D.Carosella,
P.Moreau,
J.Lemaoult,
and
N.Rouas-Freiss
(2008).
HLA-G: from biology to clinical benefits.
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Trends Immunol,
29,
125-132.
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K.S.Famulski,
B.Sis,
L.Billesberger,
and
P.F.Halloran
(2008).
Interferon-gamma and donor MHC class I control alternative macrophage activation and activin expression in rejecting kidney allografts: a shift in the Th1-Th2 paradigm.
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Am J Transplant,
8,
547-556.
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P.W.Lampton,
C.Y.Goldstein,
and
C.M.Warner
(2008).
The role of tapasin in MHC class I protein trafficking in embryos and T cells.
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J Reprod Immunol,
78,
28-39.
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R.Apps,
L.Gardner,
and
A.Moffett
(2008).
A critical look at HLA-G.
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Trends Immunol,
29,
313-321.
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R.H.McIntire,
T.Sifers,
J.S.Platt,
K.G.Ganacias,
D.K.Langat,
and
J.S.Hunt
(2008).
Novel HLA-G-binding leukocyte immunoglobulin-like receptor (LILR) expression patterns in human placentas and umbilical cords.
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Placenta,
29,
631-638.
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S.Liang,
V.Ristich,
H.Arase,
J.Dausset,
E.D.Carosella,
and
A.Horuzsko
(2008).
Modulation of dendritic cell differentiation by HLA-G and ILT4 requires the IL-6--STAT3 signaling pathway.
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Proc Natl Acad Sci U S A,
105,
8357-8362.
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W.H.Yan,
A.Lin,
B.G.Chen,
W.D.Luo,
M.Z.Dai,
X.J.Chen,
H.H.Xu,
and
B.L.Li
(2008).
Unfavourable clinical implications for HLA-G expression in acute myeloid leukaemia.
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J Cell Mol Med,
12,
889-898.
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Z.Yang,
and
P.J.Bjorkman
(2008).
Structure of UL18, a peptide-binding viral MHC mimic, bound to a host inhibitory receptor.
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Proc Natl Acad Sci U S A,
105,
10095-10100.
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PDB code:
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J.S.Hunt,
P.J.Morales,
J.L.Pace,
A.T.Fazleabas,
and
D.K.Langat
(2007).
A commentary on gestational programming and functions of HLA-G in pregnancy.
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Placenta,
28,
S57-S63.
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J.Wischhusen,
A.Waschbisch,
and
H.Wiendl
(2007).
Immune-refractory cancers and their little helpers--an extended role for immunetolerogenic MHC molecules HLA-G and HLA-E?
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Semin Cancer Biol,
17,
459-468.
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K.Kuroki,
and
K.Maenaka
(2007).
Immune modulation of HLA-G dimer in maternal-fetal interface.
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Eur J Immunol,
37,
1727-1729.
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M.D.Crew
(2007).
Play it in E or G: utilization of HLA-E and -G in xenotransplantation.
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Xenotransplantation,
14,
198-207.
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M.Lichterfeld,
D.G.Kavanagh,
K.L.Williams,
B.Moza,
S.K.Mui,
T.Miura,
R.Sivamurthy,
R.Allgaier,
F.Pereyra,
A.Trocha,
M.Feeney,
R.T.Gandhi,
E.S.Rosenberg,
M.Altfeld,
T.M.Allen,
R.Allen,
B.D.Walker,
E.J.Sundberg,
and
X.G.Yu
(2007).
A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells.
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J Exp Med,
204,
2813-2824.
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P.J.Morales,
J.L.Pace,
J.S.Platt,
D.K.Langat,
and
J.S.Hunt
(2007).
Synthesis of beta(2)-microglobulin-free, disulphide-linked HLA-G5 homodimers in human placental villous cytotrophoblast cells.
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Immunology,
122,
179-188.
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R.L.Rich,
and
D.G.Myszka
(2007).
Survey of the year 2006 commercial optical biosensor literature.
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J Mol Recognit,
20,
300-366.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
