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Signaling protein
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PDB id
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2gy7
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Contents |
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* Residue conservation analysis
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Enzyme class:
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Chain B:
E.C.2.7.10.1
- Receptor protein-tyrosine kinase.
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Reaction:
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ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
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ATP
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+
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[protein]-L-tyrosine
Bound ligand (Het Group name = )
matches with 47.62% similarity
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=
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ADP
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+
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[protein]-L-tyrosine phosphate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular space
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2 terms
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Biological process
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signal transduction
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3 terms
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Biochemical function
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protein binding
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4 terms
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DOI no:
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Nat Struct Mol Biol
13:524-532
(2006)
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PubMed id:
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Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex.
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W.A.Barton,
D.Tzvetkova-Robev,
E.P.Miranda,
M.V.Kolev,
K.R.Rajashankar,
J.P.Himanen,
D.B.Nikolov.
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ABSTRACT
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The Tie receptor tyrosine kinases and their angiopoietin (Ang) ligands play
central roles in developmental and tumor-induced angiogenesis. Here we present
the crystal structures of the Tie2 ligand-binding region alone and in complex
with Ang2. In contrast to prediction, Tie2 contains not two but three
immunoglobulin (Ig) domains, which fold together with the three epidermal growth
factor domains into a compact, arrowhead-shaped structure. Ang2 binds at the tip
of the arrowhead utilizing a lock-and-key mode of ligand recognition-unique for
a receptor kinase-where two complementary surfaces interact with each other with
no domain rearrangements and little conformational change in either molecule.
Ang2-Tie2 recognition is similar to antibody-protein antigen recognition,
including the location of the ligand-binding site within the Ig fold. Analysis
of the structures and structure-based mutagenesis provide insight into the
mechanism of receptor activation and support the hypothesis that all
angiopoietins interact with Tie2 in a structurally similar manner.
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Selected figure(s)
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Figure 1.
Figure 1. Structure of the Tie2 ligand-binding region. (a)
Schematic representation of the domain organization of the Tie
receptors. Red, Ig1; blue, Ig2; green, Ig3; yellow, EGF1;
purple, EGF2; orange, EGF3; gray, the three fibronectin type III
(FNIII) repeats and the cytoplasmic tyrosine kinase catalytic
domain. (b) The ligand-binding extracellular region of Tie2,
colored as in a. Asparagine-linked carbohydrate groups are shown
in ball-and-stick format. (c) The EGF region of Tie2, colored as
in a. The 12 disulfide bonds (four in each EGF repeat) are shown
in gray ball-and-stick format. (d) The Tie2 ligand-binding
region. Red, the large and highly curved trans-domain
11-stranded  -sheet
comprised of strands Ig1(D-E-B-A-)-EGF2(C-D)-Ig2(A'-G-F-C-C').
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Figure 4.
Figure 4. Crystal structure of the Ang2–Tie2 complex. Shown
are two views of the complex related by a 90° rotation
around the y-axis. Yellow, P domain of Ang2; red, the rest of
Ang2; green, Tie2 Ig2; blue, the rest of Tie2; black sphere,
bound Ca^2+. Asparagine-linked carbohydrate groups are shown in
ball-and-stick format.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2006,
13,
524-532)
copyright 2006.
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Figures were
selected
by the author.
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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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H.Huang,
A.Bhat,
G.Woodnutt,
and
R.Lappe
(2010).
Targeting the ANGPT-TIE2 pathway in malignancy.
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Nat Rev Cancer, 10,
575-585.
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T.C.Seegar,
B.Eller,
D.Tzvetkova-Robev,
M.V.Kolev,
S.C.Henderson,
D.B.Nikolov,
and
W.A.Barton
(2010).
Tie1-Tie2 interactions mediate functional differences between angiopoietin ligands.
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Mol Cell, 37,
643-655.
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T.M.Hansen,
H.Singh,
T.A.Tahir,
and
N.P.Brindle
(2010).
Effects of angiopoietins-1 and -2 on the receptor tyrosine kinase Tie2 are differentially regulated at the endothelial cell surface.
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Cell Signal, 22,
527-532.
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H.G.Augustin,
G.Young Koh,
G.Thurston,
and
K.Alitalo
(2009).
Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system.
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Nat Rev Mol Cell Biol, 10,
165-177.
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R.Mor-Cohen,
N.Rosenberg,
M.Landau,
J.Lahav,
and
U.Seligsohn
(2008).
Specific cysteines in beta3 are involved in disulfide bond exchange-dependent and -independent activation of alphaIIbbeta3.
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J Biol Chem, 283,
19235-19244.
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T.Makinde,
and
D.K.Agrawal
(2008).
Intra and extravascular transmembrane signalling of angiopoietin-1-Tie2 receptor in health and disease.
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J Cell Mol Med, 12,
810-828.
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V.P.Nguyen,
S.H.Chen,
J.Trinh,
H.Kim,
B.L.Coomber,
and
D.J.Dumont
(2007).
Differential response of lymphatic, venous and arterial endothelial cells to angiopoietin-1 and angiopoietin-2.
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BMC Cell Biol, 8,
10.
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P.R.Macdonald,
P.Progias,
B.Ciani,
S.Patel,
U.Mayer,
M.O.Steinmetz,
and
R.A.Kammerer
(2006).
Structure of the extracellular domain of Tie receptor tyrosine kinases and localization of the angiopoietin-binding epitope.
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J Biol Chem, 281,
28408-28414.
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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.
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Links
