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PDBsum entry 1dev
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Signaling protein
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PDB id
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1dev
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural basis of smad2 recognition by the smad anchor for receptor activation.
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Authors
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G.Wu,
Y.G.Chen,
B.Ozdamar,
C.A.Gyuricza,
P.A.Chong,
J.L.Wrana,
J.Massagué,
Y.Shi.
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Ref.
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Science, 2000,
287,
92-97.
[DOI no: ]
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PubMed id
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Abstract
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The Smad proteins mediate transforming growth factor-beta (TGFbeta) signaling
from the transmembrane serine-threonine receptor kinases to the nucleus. The
Smad anchor for receptor activation (SARA) recruits Smad2 to the TGFbeta
receptors for phosphorylation. The crystal structure of a Smad2 MH2 domain in
complex with the Smad-binding domain (SBD) of SARA has been determined at 2.2
angstrom resolution. SARA SBD, in an extended conformation comprising a rigid
coil, an alpha helix, and a beta strand, interacts with the beta sheet and the
three-helix bundle of Smad2. Recognition between the SARA rigid coil and the
Smad2 beta sheet is essential for specificity, whereas interactions between the
SARA beta strand and the Smad2 three-helix bundle contribute significantly to
binding affinity. Comparison of the structures between Smad2 and a comediator
Smad suggests a model for how receptor-regulated Smads are recognized by the
type I receptors.
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Figure 2.
Fig. 2. Overall structure of the Smad2 MH2 domain in complex
with a SARA SBD. (A) The schematic representation on the right
panel is related to the one on the left by a 90° rotation
along the horizontal axis. Smad2 and SARA are shown in green and
pink, respectively. The secondary structural elements in SARA
and some prominent features in Smad2 are labeled and
color-coded. (B) Sequence of the SARA SBD showing its secondary
structural elements. The bar graph below sequence shows the
buried surface area per SARA residue upon complex formation. The
residues that are targeted by inactivating mutations are
highlighted in red (Fig. 1C). (C) Superimposition of the
structures of the MH2 domains in Smad2 (green) and Smad4 (red),
shown in stereo view. The disordered loop between helices H3 and
H4 in Smad4 is indicated by a red dotted line. This figure was
prepared with MOLSCRIPT (24).
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Figure 3.
Fig. 3. Schematic representation of the interactions between
Smad2 and SARA. (A) The interactions are predominantly
hydrophobic in nature. The surface of Smad2 MH2 domain is
represented by degrees of hydrophobicity. The C  backbone
of SARA SBD is shown in pink and the buried hydrophobic residues
are highlighted in orange. This figure was prepared with GRASP
(25). (B) A closeup view of the interactions between the rigid
coil of SARA and the strands B8 and B9 of Smad2. Smad2 and SARA
are colored green and pink, respectively. The interacting side
chains are shown in yellow for Smad2 and in purple for SARA. The
O and N atoms are shown as red and blue balls, respectively. The
left panel shows the interface, whereas the right panel shows
the conformation of the rigid coil by itself. Aside from
extensive van der Waals interactions at the interface, there are
a total of five intermolecular H bonds. These include: Ser671 O
 to Tyr366
carbonyl, Pro672 carbonyl to Trp368 N  1, Tyr680
O  to Lys375
amide, Ser682 amide to Asn381 carbonyl, and Ser682 carbonyl to
Asn381 amide. (C) A closeup view of the interactions between the
helix of
SARA and strands B5 and B6 of Smad2. Color coding scheme is
identical to (B). (D) A closeup view of the interactions between
the  strand of
SARA and the three-helix bundle and strand B1' of Smad2.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2000,
287,
92-97)
copyright 2000.
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