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PDBsum entry 2fd6
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Immune system, hydrolase
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PDB id
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2fd6
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Contents |
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122 a.a.
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214 a.a.
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212 a.a.
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249 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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Structure of human urokinase plasminogen activator in complex with its receptor.
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Authors
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Q.Huai,
A.P.Mazar,
A.Kuo,
G.C.Parry,
D.E.Shaw,
J.Callahan,
Y.Li,
C.Yuan,
C.Bian,
L.Chen,
B.Furie,
B.C.Furie,
D.B.Cines,
M.Huang.
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Ref.
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Science, 2006,
311,
656-659.
[DOI no: ]
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PubMed id
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Abstract
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The urokinase plasminogen activator binds to its cellular receptor with high
affinity and initiates signaling cascades that are implicated in pathological
processes including tumor growth, metastasis, and inflammation. We report the
crystal structure at 1.9 angstroms of the urokinase receptor complexed with the
urokinase amino-terminal fragment and an antibody against the receptor. The
three domains of urokinase receptor form a concave shape with a central
cone-shaped cavity where the urokinase fragment inserts. The structure provides
insight into the flexibility of the urokinase receptor that enables its
interaction with a wide variety of ligands and a basis for the design of
urokinase-urokinase receptor antagonists.
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Figure 1.
Fig. 1. X-ray structure of the suPAR-ATF-ATN615 complex. (A)
Stereo view of the structure of the suPAR-ATF-ATN615 complex. In
the ribbon diagram of the ternary complex, the D1 domain of
suPAR is shown in orange, the D2 domain in magenta, and the D3
domain in green. The ATF is shown in cyan, light chain of the
antibody ATN615 in light blue, and the heavy chain in dark blue.
Carbohydrates in suPAR are shown as red sticks. Disulfide bonds
are shown in dashed lines colored as is the backbone to which
they are attached. (B) Ribbon structure of ATF. The GFD domain
is shown in cyan and the kringle domain in dark salmon. The
residues Leu14, His41, Ile^44, Asp45, Arg59, Leu92, and Tyr101
involved in domain interactions are shown as sticks.  -loop (residues
23 to 29) connects two ß strands (residues 18 to 22 and 30
to 32) in the GFD domain. The kringle domain contains two
strands (residues 112 to 117 and 120 to 125) and two short  helices (78 to 81
and 91 to 94). All figures were made by PyMOL (23).
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Figure 3.
Fig. 3. The suPAR-ATF binding surface. The carbon atoms of the
D1 domain of uPAR are shown in orange, the D2 in magenta, and
the D3 in orange. The ATF is shown in a ribbon diagram in cyan.
(A) Molecular surface representation of the overall suPAR-ATF
binding. The three uPAR domains form a conical cavity with a
wide opening (25 Å) and large depth (14 Å) that are
involved in the ATF binding. (B) Surface representation of the
uPAR-ATF binding. The circled areas are regions 1 and 2 (from
left to right) of uPAR-ATF interface. Oxygen atoms are shown in
red, nitrogen atoms in blue, and sulfur in yellow. Waters
involved in uPAR-ATF binding are shown as red spheres. Hydrogen
bonds are shown as dashed lines (light blue). (C) Detailed
interaction of suPAR (ribbon representation) and the ATF in
stereoview. Thr8, Arg53, Glu68, Thr127, and His166 of suPAR form
hydrogen bonds with Ser21, Lys23, Tyr24, Ser26, and Gln40 of
ATF.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2006,
311,
656-659)
copyright 2006.
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