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PDBsum entry 1dr9
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Immune system
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PDB id
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1dr9
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Contents |
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* Residue conservation analysis
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DOI no:
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Immunity
12:51-60
(2000)
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PubMed id:
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Structure and dimerization of a soluble form of B7-1.
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S.Ikemizu,
R.J.Gilbert,
J.A.Fennelly,
A.V.Collins,
K.Harlos,
E.Y.Jones,
D.I.Stuart,
S.J.Davis.
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ABSTRACT
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B7-1 (CD80) and B7-2 (CD86) are glycoproteins expressed on antigen-presenting
cells. The binding of these molecules to the T cell homodimers CD28 and CTLA-4
(CD152) generates costimulatory and inhibitory signals in T cells, respectively.
The crystal structure of the extracellular region of B7-1 (sB7-1), solved to 3 A
resolution, consists of a novel combination of two Ig-like domains, one
characteristic of adhesion molecules and the other previously seen only in
antigen receptors. In the crystal lattice, sB7-1 unexpectedly forms parallel,
2-fold rotationally symmetric homodimers. Analytical ultracentrifugation reveals
that sB7-1 also dimerizes in solution. The structural data suggest a mechanism
whereby the avidity-enhanced binding of B7-1 and CTLA-4 homodimers, along with
the relatively high affinity of these interactions, favors the formation of very
stable inhibitory signaling complexes.
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Selected figure(s)
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Figure 4.
Figure 4. Structure of the sB7-1 Homodimer Observed in the
Crystal Lattice(A) Two orthogonal views of the GRASP surface of
the homodimer showing the location of residues whose mutation to
alanine disrupts (magenta) or has no effect (cyan) on binding.
Putative N-glycosylation sites are colored green.(B) The GRASP
surfaces of amino acids involved in forming the dimer are
colored red. The view is identical to the right-hand panel in
(A) but with the front copy of sB7-1 removed.(C) Details of the
residues at the dimer interface are shown in ball-and-stick
format viewed as in the left-hand panel of (A).(D) The homodimer
is shown with either oligomannose, bi-, or triantennary
N-glycans modeled at each of the potential glycosylation sites.
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Figure 6.
Figure 6. Evolutionary Relationships of the IgSF
Constant-like DomainsThe parts of the lineage colored blue are
proposed to have generated cell adhesion and cell–cell
recognition molecules, whereas the red section produced
components of the adaptive immune response. CD2 is used to
represent the C2/I-set.
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The above figures are
reprinted
by permission from Cell Press:
Immunity
(2000,
12,
51-60)
copyright 2000.
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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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L.S.Walker,
and
D.M.Sansom
(2011).
The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses.
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Nat Rev Immunol,
11,
852-863.
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Y.Li,
Q.Wang,
and
R.A.Mariuzza
(2011).
Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6.
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J Exp Med,
208,
703-714.
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C.E.Rudd,
A.Taylor,
and
H.Schneider
(2009).
CD28 and CTLA-4 coreceptor expression and signal transduction.
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Immunol Rev,
229,
12-26.
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D.Hatherley,
S.C.Graham,
K.Harlos,
D.I.Stuart,
and
A.N.Barclay
(2009).
Structure of signal-regulatory protein alpha: a link to antigen receptor evolution.
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J Biol Chem,
284,
26613-26619.
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PDB code:
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H.Bour-Jordan,
and
J.A.Bluestone
(2009).
Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cells.
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Immunol Rev,
229,
41-66.
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K.Chattopadhyay,
E.Lazar-Molnar,
Q.Yan,
R.Rubinstein,
C.Zhan,
V.Vigdorovich,
U.A.Ramagopal,
J.Bonanno,
S.G.Nathenson,
and
S.C.Almo
(2009).
Sequence, structure, function, immunity: structural genomics of costimulation.
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Immunol Rev,
229,
356-386.
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K.G.Haanstra,
J.Endell,
D.Estévâo,
I.Kondova,
and
M.Jonker
(2009).
Blocking T cell co-stimulation using a CD80 blocking small molecule reduces delayed type hypersensitivity responses in rhesus monkeys.
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Clin Exp Immunol,
158,
91-98.
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T.Pentcheva-Hoang,
E.Corse,
and
J.P.Allison
(2009).
Negative regulators of T-cell activation: potential targets for therapeutic intervention in cancer, autoimmune disease, and persistent infections.
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Immunol Rev,
229,
67-87.
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T.Yokosuka,
and
T.Saito
(2009).
Dynamic regulation of T-cell costimulation through TCR-CD28 microclusters.
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Immunol Rev,
229,
27-40.
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E.Lázár-Molnár,
Q.Yan,
E.Cao,
U.Ramagopal,
S.G.Nathenson,
and
S.C.Almo
(2008).
Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2.
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Proc Natl Acad Sci U S A,
105,
10483-10488.
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PDB codes:
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G.J.Freeman
(2008).
Structures of PD-1 with its ligands: sideways and dancing cheek to cheek.
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Proc Natl Acad Sci U S A,
105,
10275-10276.
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N.Perez,
S.Karumuthil-Melethil,
R.Li,
B.S.Prabhakar,
M.J.Holterman,
and
C.Vasu
(2008).
Preferential costimulation by CD80 results in IL-10-dependent TGF-beta1(+) -adaptive regulatory T cell generation.
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J Immunol,
180,
6566-6576.
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S.N.Shen,
Z.Xu,
X.P.Qian,
Y.T.Ding,
L.X.Yu,
and
B.R.Liu
(2008).
RNA-electroporated CD40-activated B cells induce functional T-cell responses against HepG2 cells.
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Eur J Cancer Care (Engl),
17,
404-411.
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X.L.Yu,
T.Hu,
J.M.Du,
J.P.Ding,
X.M.Yang,
J.Zhang,
B.Yang,
X.Shen,
Z.Zhang,
W.D.Zhong,
N.Wen,
H.Jiang,
P.Zhu,
and
Z.N.Chen
(2008).
Crystal structure of HAb18G/CD147: implications for immunoglobulin superfamily homophilic adhesion.
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J Biol Chem,
283,
18056-18065.
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PDB code:
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M.J.Butte,
M.E.Keir,
T.B.Phamduy,
A.H.Sharpe,
and
G.J.Freeman
(2007).
Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses.
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Immunity,
27,
111-122.
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A.Geerlof,
J.Brown,
B.Coutard,
M.P.Egloff,
F.J.Enguita,
M.J.Fogg,
R.J.Gilbert,
M.R.Groves,
A.Haouz,
J.E.Nettleship,
P.Nordlund,
R.J.Owens,
M.Ruff,
S.Sainsbury,
D.I.Svergun,
and
M.Wilmanns
(2006).
The impact of protein characterization in structural proteomics.
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Acta Crystallogr D Biol Crystallogr,
62,
1125-1136.
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D.M.Sansom,
and
L.S.Walker
(2006).
The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T-cell biology.
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Immunol Rev,
212,
131-148.
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J.R.James,
M.I.Oliveira,
A.M.Carmo,
A.Iaboni,
and
S.J.Davis
(2006).
A rigorous experimental framework for detecting protein oligomerization using bioluminescence resonance energy transfer.
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Nat Methods,
3,
1001-1006.
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Y.Q.Chen,
and
H.Z.Shi
(2006).
CD28/CTLA-4--CD80/CD86 and ICOS--B7RP-1 costimulatory pathway in bronchial asthma.
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Allergy,
61,
15-26.
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C.Lamagna,
P.Meda,
G.Mandicourt,
J.Brown,
R.J.Gilbert,
E.Y.Jones,
F.Kiefer,
P.Ruga,
B.A.Imhof,
and
M.Aurrand-Lions
(2005).
Dual interaction of JAM-C with JAM-B and alpha(M)beta2 integrin: function in junctional complexes and leukocyte adhesion.
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Mol Biol Cell,
16,
4992-5003.
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E.J.Evans,
R.M.Esnouf,
R.Manso-Sancho,
R.J.Gilbert,
J.R.James,
C.Yu,
J.A.Fennelly,
C.Vowles,
T.Hanke,
B.Walse,
T.Hünig,
P.Sørensen,
D.I.Stuart,
and
S.J.Davis
(2005).
Crystal structure of a soluble CD28-Fab complex.
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Nat Immunol,
6,
271-279.
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PDB code:
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M.Collins,
V.Ling,
and
B.M.Carreno
(2005).
The B7 family of immune-regulatory ligands.
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Genome Biol,
6,
223.
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M.Srinivasan,
D.Lu,
R.Eri,
D.D.Brand,
A.Haque,
and
J.S.Blum
(2005).
CD80 binding polyproline helical peptide inhibits T cell activation.
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J Biol Chem,
280,
10149-10155.
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R.Valentonyte,
J.Hampe,
K.Huse,
P.Rosenstiel,
M.Albrecht,
A.Stenzel,
M.Nagy,
K.I.Gaede,
A.Franke,
R.Haesler,
A.Koch,
T.Lengauer,
D.Seegert,
N.Reiling,
S.Ehlers,
E.Schwinger,
M.Platzer,
M.Krawczak,
J.Müller-Quernheim,
M.Schürmann,
and
S.Schreiber
(2005).
Sarcoidosis is associated with a truncating splice site mutation in BTNL2.
|
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Nat Genet,
37,
357-364.
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S.Bhatia,
M.Edidin,
S.C.Almo,
and
S.G.Nathenson
(2005).
Different cell surface oligomeric states of B7-1 and B7-2: implications for signaling.
|
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Proc Natl Acad Sci U S A,
102,
15569-15574.
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S.C.Gough,
L.S.Walker,
and
D.M.Sansom
(2005).
CTLA4 gene polymorphism and autoimmunity.
|
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Immunol Rev,
204,
102-115.
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T.Okazaki,
and
J.Wang
(2005).
PD-1/PD-L pathway and autoimmunity.
|
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Autoimmunity,
38,
353-357.
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X.Y.Zhu,
Y.H.Zhou,
M.Y.Wang,
L.P.Jin,
M.M.Yuan,
and
D.J.Li
(2005).
Blockade of CD86 signaling facilitates a Th2 bias at the maternal-fetal interface and expands peripheral CD4+CD25+ regulatory T cells to rescue abortion-prone fetuses.
|
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Biol Reprod,
72,
338-345.
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G.Sutton,
E.Fry,
L.Carter,
S.Sainsbury,
T.Walter,
J.Nettleship,
N.Berrow,
R.Owens,
R.Gilbert,
A.Davidson,
S.Siddell,
L.L.Poon,
J.Diprose,
D.Alderton,
M.Walsh,
J.M.Grimes,
and
D.I.Stuart
(2004).
The nsp9 replicase protein of SARS-coronavirus, structure and functional insights.
|
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Structure,
12,
341-353.
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PDB code:
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H.Z.Shi,
Z.F.Xie,
J.M.Deng,
Y.Q.Chen,
and
C.Q.Xiao
(2004).
Soluble CD86 protein in serum samples of patients with asthma.
|
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Thorax,
59,
870-875.
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L.Du Pasquier,
I.Zucchetti,
and
R.De Santis
(2004).
Immunoglobulin superfamily receptors in protochordates: before RAG time.
|
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Immunol Rev,
198,
233-248.
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M.C.Brunner-Weinzierl,
H.Hoff,
and
G.R.Burmester
(2004).
Multiple functions for CD28 and cytotoxic T lymphocyte antigen-4 during different phases of T cell responses: implications for arthritis and autoimmune diseases.
|
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Arthritis Res Ther,
6,
45-54.
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M.Kasahara,
T.Suzuki,
and
L.D.Pasquier
(2004).
On the origins of the adaptive immune system: novel insights from invertebrates and cold-blooded vertebrates.
|
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Trends Immunol,
25,
105-111.
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M.R.Arkin,
and
J.A.Wells
(2004).
Small-molecule inhibitors of protein-protein interactions: progressing towards the dream.
|
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Nat Rev Drug Discov,
3,
301-317.
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B.P.Nayak,
G.Sailaja,
and
A.M.Jabbar
(2003).
Enhancement of gp120-specific immune responses by genetic vaccination with the human immunodeficiency virus type 1 envelope gene fused to the gene coding for soluble CTLA4.
|
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J Virol,
77,
10850-10861.
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C.E.Rudd,
and
H.Schneider
(2003).
Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling.
|
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Nat Rev Immunol,
3,
544-556.
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D.M.Sansom,
C.N.Manzotti,
and
Y.Zheng
(2003).
What's the difference between CD80 and CD86?
|
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Trends Immunol,
24,
314-319.
|
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F.Lühder,
Y.Huang,
K.M.Dennehy,
C.Guntermann,
I.Müller,
E.Winkler,
T.Kerkau,
S.Ikemizu,
S.J.Davis,
T.Hanke,
and
T.Hünig
(2003).
Topological requirements and signaling properties of T cell-activating, anti-CD28 antibody superagonists.
|
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J Exp Med,
197,
955-966.
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J.H.Wang,
and
M.J.Eck
(2003).
Assembling atomic resolution views of the immunological synapse.
|
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Curr Opin Immunol,
15,
286-293.
|
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K.G.Haanstra,
J.Ringers,
E.A.Sick,
S.Ramdien-Murli,
E.M.Kuhn,
L.Boon,
and
M.Jonker
(2003).
Prevention of kidney allograft rejection using anti-CD40 and anti-CD86 in primates.
|
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Transplantation,
75,
637-643.
|
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M.Harkiolaki,
M.Lewitzky,
R.J.Gilbert,
E.Y.Jones,
R.P.Bourette,
G.Mouchiroud,
H.Sondermann,
I.Moarefi,
and
S.M.Feller
(2003).
Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76.
|
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EMBO J,
22,
2571-2582.
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PDB code:
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P.A.van der Merwe,
and
S.J.Davis
(2003).
Molecular interactions mediating T cell antigen recognition.
|
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Annu Rev Immunol,
21,
659-684.
|
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S.Wang,
J.Bajorath,
D.B.Flies,
H.Dong,
T.Honjo,
and
L.Chen
(2003).
Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction.
|
| |
J Exp Med,
197,
1083-1091.
|
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X.Zhang,
J.C.Schwartz,
S.C.Almo,
and
S.G.Nathenson
(2003).
Crystal structure of the receptor-binding domain of human B7-2: insights into organization and signaling.
|
| |
Proc Natl Acad Sci U S A,
100,
2586-2591.
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PDB code:
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A.H.Sharpe,
and
G.J.Freeman
(2002).
The B7-CD28 superfamily.
|
| |
Nat Rev Immunol,
2,
116-126.
|
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A.V.Collins,
D.W.Brodie,
R.J.Gilbert,
A.Iaboni,
R.Manso-Sancho,
B.Walse,
D.I.Stuart,
P.A.van der Merwe,
and
S.J.Davis
(2002).
The interaction properties of costimulatory molecules revisited.
|
| |
Immunity,
17,
201-210.
|
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|
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B.M.Carreno,
and
M.Collins
(2002).
The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses.
|
| |
Annu Rev Immunol,
20,
29-53.
|
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D.V.Erbe,
S.Wang,
Y.Xing,
and
J.F.Tobin
(2002).
Small molecule ligands define a binding site on the immune regulatory protein B7.1.
|
| |
J Biol Chem,
277,
7363-7368.
|
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M.S.Teng,
R.Stephens,
L.Du Pasquier,
T.Freeman,
J.A.Lindquist,
and
J.Trowsdale
(2002).
A human TAPBP (TAPASIN)-related gene, TAPBP-R.
|
| |
Eur J Immunol,
32,
1059-1068.
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R.J.Greenwald,
Y.E.Latchman,
and
A.H.Sharpe
(2002).
Negative co-receptors on lymphocytes.
|
| |
Curr Opin Immunol,
14,
391-396.
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R.W.Stuart,
and
M.K.Racke
(2002).
Targeting T cell costimulation in autoimmune disease.
|
| |
Expert Opin Ther Targets,
6,
275-289.
|
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S.Suvas,
V.Singh,
S.Sahdev,
H.Vohra,
and
J.N.Agrewala
(2002).
Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma.
|
| |
J Biol Chem,
277,
7766-7775.
|
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A.Carfí,
S.H.Willis,
J.C.Whitbeck,
C.Krummenacher,
G.H.Cohen,
R.J.Eisenberg,
and
D.C.Wiley
(2001).
Herpes simplex virus glycoprotein D bound to the human receptor HveA.
|
| |
Mol Cell,
8,
169-179.
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PDB codes:
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B.Salomon,
and
J.A.Bluestone
(2001).
Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation.
|
| |
Annu Rev Immunol,
19,
225-252.
|
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C.A.Chambers,
M.S.Kuhns,
J.G.Egen,
and
J.P.Allison
(2001).
CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy.
|
| |
Annu Rev Immunol,
19,
565-594.
|
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C.A.Chambers
(2001).
The expanding world of co-stimulation: the two-signal model revisited.
|
| |
Trends Immunol,
22,
217-223.
|
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C.L.Van Broekhoven,
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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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