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276 a.a.
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93 a.a.
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183 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 hla-a2 bound to lir-1, a host and viral mhc receptor
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Structure:
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Hla class i histocompatibility antigen, a-2 alpha chain. Chain: a. Fragment: residue 25-300. Engineered: yes. Beta-2-microglobulin. Chain: b. Synonym: hdcma22p. Engineered: yes. Pol polyprotein.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-a or hlaa. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m. Synthetic: yes.
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Biol. unit:
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Octamer (from
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Resolution:
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3.40Å
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R-factor:
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0.218
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R-free:
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0.309
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Authors:
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B.E.Willcox,L.M.Thomas,P.J.Bjorkman
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Key ref:
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B.E.Willcox
et al.
(2003).
Crystal structure of HLA-A2 bound to LIR-1, a host and viral major histocompatibility complex receptor.
Nat Immunol,
4,
913-919.
PubMed id:
DOI:
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Date:
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05-May-03
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Release date:
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14-Oct-03
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PROCHECK
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Headers
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References
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P04439
(1A03_HUMAN) -
HLA class I histocompatibility antigen, A alpha chain from Homo sapiens
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Seq:
Struc:
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365 a.a.
276 a.a.*
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DOI no:
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Nat Immunol
4:913-919
(2003)
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PubMed id:
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Crystal structure of HLA-A2 bound to LIR-1, a host and viral major histocompatibility complex receptor.
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B.E.Willcox,
L.M.Thomas,
P.J.Bjorkman.
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ABSTRACT
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Leukocyte immunoglobulin-like receptor 1 (LIR-1), an inhibitory receptor
expressed on monocytes, dendritic cells and lymphocytes, regulates cellular
function by binding a broad range of classical and nonclassical major
histocompatibility complex (MHC) class I molecules, and the human
cytomegalovirus MHC class I homolog UL18. Here we describe the 3.4-A crystal
structure of a complex between the LIR-1 D1D2 domains and the MHC class I
molecule HLA-A2. LIR-1 contacts the mostly conserved beta(2)-microglobulin and
alpha3 domains of HLA-A2. The LIR-1 binding site comprises residues at the
interdomain hinge, and a patch at the D1 tip. The structure shows how LIR-1
recognizes UL18 and diverse MHC class I molecules, and indicates that a similar
mode of MHC class I recognition is used by other LIR family members.
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Selected figure(s)
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Figure 2.
Figure 2. Interaction surfaces used by LIR-1 and HLA-A2.
Grasp38 representations of the D1D2 -HLA-A2 structure (center),
with D1D2 contact sites (yellow) on HLA-A2 (left), and HLA-A2
contact sites (yellow) on D1D2 (right).
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Figure 4.
Figure 4. Implications of UL18 -LIR-1 interaction. (a) View
of D1D2 -HLA-A2 structure with the approximate positions of
potential UL18 glycosylation sites mapped onto the HLA-A2
structure. Potential N-linked glycosylation sites (pink spheres)
are distant from the LIR-1 binding site. The closest predicted
O-linked glycosylation site (gray sphere) is also distant from
the binding site. Three additional O-linked glycosylation sites
are predicted in UL18 in a region corresponding to sequence
between the carboxyl terminus of the HLA-A2 ectodomain and the
transmembrane region. (b) Closer view of the LIR-1 -HLA-A2
interface in the region outlined by the dotted rectangle in a.
The structures of free LIR-1 (ref. 11) and LIR-2 (ref. 17) are
superimposed on the bound LIR-1 structure to show movement of
the loop of residues 76 -84 (mostly disordered in the bound
LIR-1 structure (see Methods). The side chains of LIR-1 Asp80
(which have been linked to the binding of LIR-1 UL18; ref. 11)
and its counterpart in LIR-2, Arg80, are shown as ball-and-stick
representation.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Immunol
(2003,
4,
913-919)
copyright 2003.
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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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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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K.Köhler,
S.Xiong,
J.Brzostek,
M.Mehrabi,
P.Eissmann,
A.Harrison,
S.P.Cordoba,
S.Oddos,
V.Miloserdov,
K.Gould,
N.J.Burroughs,
P.A.van der Merwe,
and
D.M.Davis
(2010).
Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells.
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PLoS One,
5,
e15374.
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R.K.Moysey,
Y.Li,
S.J.Paston,
E.E.Baston,
M.S.Sami,
B.J.Cameron,
J.Gavarret,
P.Todorov,
A.Vuidepot,
S.M.Dunn,
N.J.Pumphrey,
K.J.Adams,
F.Yuan,
R.E.Dennis,
D.H.Sutton,
A.D.Johnson,
J.E.Brewer,
R.Ashfield,
N.M.Lissin,
and
B.K.Jakobsen
(2010).
High affinity soluble ILT2 receptor: a potent inhibitor of CD8(+) T cell activation.
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Protein Cell,
1,
1118-1127.
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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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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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H.K.Lu,
C.Rentero,
M.J.Raftery,
L.Borges,
K.Bryant,
and
N.Tedla
(2009).
Leukocyte Ig-like receptor B4 (LILRB4) is a potent inhibitor of FcgammaRI-mediated monocyte activation via dephosphorylation of multiple kinases.
|
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J Biol Chem,
284,
34839-34848.
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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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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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Y.Li,
M.Hofmann,
Q.Wang,
L.Teng,
L.K.Chlewicki,
H.Pircher,
and
R.A.Mariuzza
(2009).
Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition.
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Immunity,
31,
35-46.
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PDB codes:
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B.Sanjanwala,
M.Draghi,
P.J.Norman,
L.A.Guethlein,
and
P.Parham
(2008).
Polymorphic sites away from the Bw4 epitope that affect interaction of Bw4+ HLA-B with KIR3DL1.
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J Immunol,
181,
6293-6300.
|
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D.J.Gibbings,
A.F.Ghetu,
R.Dery,
and
A.D.Befus
(2008).
Macrophage migration inhibitory factor has a MHC class I-like motif and function.
|
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Scand J Immunol,
67,
121-132.
|
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G.W.Wilkinson,
P.Tomasec,
R.J.Stanton,
M.Armstrong,
V.Prod'homme,
R.Aicheler,
B.P.McSharry,
C.R.Rickards,
D.Cochrane,
S.Llewellyn-Lacey,
E.C.Wang,
C.A.Griffin,
and
A.J.Davison
(2008).
Modulation of natural killer cells by human cytomegalovirus.
|
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J Clin Virol,
41,
206-212.
|
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|
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J.Hasenkamp,
A.Borgerding,
M.Uhrberg,
C.Falk,
B.Chapuy,
G.Wulf,
W.Jung,
L.Trümper,
and
B.Glass
(2008).
Self-tolerance of human natural killer cells lacking self-HLA-specific inhibitory receptors.
|
| |
Scand J Immunol,
67,
218-229.
|
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|
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M.Morvan,
G.David,
V.Sébille,
A.Perrin,
K.Gagne,
C.Willem,
N.Kerdudou,
L.Denis,
B.Clémenceau,
G.Folléa,
J.D.Bignon,
and
C.Retière
(2008).
Autologous and allogeneic HLA KIR ligand environments and activating KIR control KIR NK-cell functions.
|
| |
Eur J Immunol,
38,
3474-3486.
|
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|
|
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|
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R.Apps,
L.Gardner,
and
A.Moffett
(2008).
A critical look at HLA-G.
|
| |
Trends Immunol,
29,
313-321.
|
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|
|
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|
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R.Das,
and
D.Baker
(2008).
Macromolecular modeling with rosetta.
|
| |
Annu Rev Biochem,
77,
363-382.
|
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|
|
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S.Endo,
Y.Sakamoto,
E.Kobayashi,
A.Nakamura,
and
T.Takai
(2008).
Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells.
|
| |
Proc Natl Acad Sci U S A,
105,
14515-14520.
|
|
|
|
|
|
|
T.I.Arnon,
J.T.Kaiser,
A.P.West,
R.Olson,
R.Diskin,
B.C.Viertlboeck,
T.W.Göbel,
and
P.J.Bjorkman
(2008).
The crystal structure of CHIR-AB1: a primordial avian classical Fc receptor.
|
| |
J Mol Biol,
381,
1012-1024.
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PDB code:
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W.Held,
and
R.A.Mariuzza
(2008).
Cis interactions of immunoreceptors with MHC and non-MHC ligands.
|
| |
Nat Rev Immunol,
8,
269-278.
|
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|
|
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|
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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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A.Masuda,
A.Nakamura,
T.Maeda,
Y.Sakamoto,
and
T.Takai
(2007).
Cis binding between inhibitory receptors and MHC class I can regulate mast cell activation.
|
| |
J Exp Med,
204,
907-920.
|
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J.L.Stafford,
E.Bengtén,
L.Du Pasquier,
N.W.Miller,
and
M.Wilson
(2007).
Channel catfish leukocyte immune-type receptors contain a putative MHC class I binding site.
|
| |
Immunogenetics,
59,
77-91.
|
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|
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|
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M.D.Crew
(2007).
Play it in E or G: utilization of HLA-E and -G in xenotransplantation.
|
| |
Xenotransplantation,
14,
198-207.
|
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|
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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.
|
| |
J Exp Med,
204,
2813-2824.
|
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|
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R.Apps,
L.Gardner,
A.M.Sharkey,
N.Holmes,
and
A.Moffett
(2007).
A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1.
|
| |
Eur J Immunol,
37,
1924-1937.
|
|
|
|
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C.Cerboni,
A.Achour,
A.Wärnmark,
M.Mousavi-Jazi,
T.Sandalova,
M.L.Hsu,
D.Cosman,
K.Kärre,
and
E.Carbone
(2006).
Spontaneous mutations in the human CMV HLA class I homologue UL18 affect its binding to the inhibitory receptor LIR-1/ILT2/CD85j.
|
| |
Eur J Immunol,
36,
732-741.
|
|
|
|
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|
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C.Thilo,
P.Berglund,
S.E.Applequist,
J.W.Yewdell,
H.G.Ljunggren,
and
A.Achour
(2006).
Dissection of the interaction of the human cytomegalovirus-derived US2 protein with major histocompatibility complex class I molecules: prominent role of a single arginine residue in human leukocyte antigen-A2.
|
| |
J Biol Chem,
281,
8950-8957.
|
|
|
|
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|
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K.Laun,
P.Coggill,
S.Palmer,
S.Sims,
Z.Ning,
J.Ragoussis,
E.Volpi,
N.Wilson,
S.Beck,
A.Ziegler,
and
A.Volz
(2006).
The leukocyte receptor complex in chicken is characterized by massive expansion and diversification of immunoglobulin-like Loci.
|
| |
PLoS Genet,
2,
e73.
|
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|
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|
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L.Deng,
and
R.A.Mariuzza
(2006).
Structural basis for recognition of MHC and MHC-like ligands by natural killer cell receptors.
|
| |
Semin Immunol,
18,
159-166.
|
|
|
|
|
|
|
M.Shiroishi,
K.Kuroki,
L.Rasubala,
K.Tsumoto,
I.Kumagai,
E.Kurimoto,
K.Kato,
D.Kohda,
and
K.Maenaka
(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.
|
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PDB code:
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M.Shiroishi,
K.Kuroki,
T.Ose,
L.Rasubala,
I.Shiratori,
H.Arase,
K.Tsumoto,
I.Kumagai,
D.Kohda,
and
K.Maenaka
(2006).
Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer.
|
| |
J Biol Chem,
281,
10439-10447.
|
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PDB code:
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M.Shiroishi,
M.Kajikawa,
K.Kuroki,
T.Ose,
D.Kohda,
and
K.Maenaka
(2006).
Crystal structure of the human monocyte-activating receptor, "Group 2" leukocyte Ig-like receptor A5 (LILRA5/LIR9/ILT11).
|
| |
J Biol Chem,
281,
19536-19544.
|
|
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PDB code:
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|
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S.Liang,
W.Zhang,
and
A.Horuzsko
(2006).
Human ILT2 receptor associates with murine MHC class I molecules in vivo and impairs T cell function.
|
| |
Eur J Immunol,
36,
2457-2471.
|
|
|
|
|
|
|
A.Nakamura,
K.Akiyama,
and
T.Takai
(2005).
Fc receptor targeting in the treatment of allergy, autoimmune diseases and cancer.
|
| |
Expert Opin Ther Targets,
9,
169-190.
|
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|
|
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|
|
C.Griffin,
E.C.Wang,
B.P.McSharry,
C.Rickards,
H.Browne,
G.W.Wilkinson,
and
P.Tomasec
(2005).
Characterization of a highly glycosylated form of the human cytomegalovirus HLA class I homologue gpUL18.
|
| |
J Gen Virol,
86,
2999-3008.
|
|
|
|
|
|
|
C.S.Clements,
L.Kjer-Nielsen,
L.Kostenko,
H.L.Hoare,
M.A.Dunstone,
E.Moses,
K.Freed,
A.G.Brooks,
J.Rossjohn,
and
J.McCluskey
(2005).
Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface.
|
| |
Proc Natl Acad Sci U S A,
102,
3360-3365.
|
|
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PDB code:
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D.Tobi,
and
I.Bahar
(2005).
Structural changes involved in protein binding correlate with intrinsic motions of proteins in the unbound state.
|
| |
Proc Natl Acad Sci U S A,
102,
18908-18913.
|
|
|
|
|
|
|
J.Cinatl,
M.Scholz,
and
H.W.Doerr
(2005).
Role of tumor cell immune escape mechanisms in cytomegalovirus-mediated oncomodulation.
|
| |
Med Res Rev,
25,
167-185.
|
|
|
|
|
|
|
M.C.Mingari,
G.Pietra,
and
L.Moretta
(2005).
Human cytolytic T lymphocytes expressing HLA class-I-specific inhibitory receptors.
|
| |
Curr Opin Immunol,
17,
312-319.
|
|
|
|
|
|
|
M.Valés-Gómez,
M.Shiroishi,
K.Maenaka,
and
H.T.Reyburn
(2005).
Genetic variability of the major histocompatibility complex class I homologue encoded by human cytomegalovirus leads to differential binding to the inhibitory receptor ILT2.
|
| |
J Virol,
79,
2251-2260.
|
|
|
|
|
|
|
T.Raine,
and
R.Allen
(2005).
MHC-I recognition by receptors on myelomonocytic cells: new tricks for old dogs?
|
| |
Bioessays,
27,
542-550.
|
|
|
|
|
|
|
A.Nakamura,
E.Kobayashi,
and
T.Takai
(2004).
Exacerbated graft-versus-host disease in Pirb-/- mice.
|
| |
Nat Immunol,
5,
623-629.
|
|
|
|
|
|
|
D.Brown,
J.Trowsdale,
and
R.Allen
(2004).
The LILR family: modulators of innate and adaptive immune pathways in health and disease.
|
| |
Tissue Antigens,
64,
215-225.
|
|
|
|
|
|
|
E.Vivier,
and
N.Anfossi
(2004).
Inhibitory NK-cell receptors on T cells: witness of the past, actors of the future.
|
| |
Nat Rev Immunol,
4,
190-198.
|
|
|
|
|
|
|
C.E.Foster,
M.Colonna,
and
P.D.Sun
(2003).
Crystal structure of the human natural killer (NK) cell activating receptor NKp46 reveals structural relationship to other leukocyte receptor complex immunoreceptors.
|
| |
J Biol Chem,
278,
46081-46086.
|
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|
PDB code:
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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
code is
shown on the right.
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Links
