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PDBsum entry 1lx5
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Growth factor/growth factor receptor
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PDB id
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1lx5
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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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The bmp7/actrii extracellular domain complex provides new insights into the cooperative nature of receptor assembly.
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Authors
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J.Greenwald,
J.Groppe,
P.Gray,
E.Wiater,
W.Kwiatkowski,
W.Vale,
S.Choe.
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Ref.
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Mol Cell, 2003,
11,
605-617.
[DOI no: ]
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PubMed id
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Abstract
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Activins and bone morphogenetic proteins (BMPs) elicit diverse biological
responses by signaling through two pairs of structurally related type I and type
II receptors. Here we report the crystal structure of BMP7 in complex with the
extracellular domain (ECD) of the activin type II receptor. Our structure
produces a compelling four-receptor model, revealing that the types I and II
receptor ECDs make no direct contacts. Nevertheless, we find that truncated
receptors lacking their cytoplasmic domain retain the ability to cooperatively
assemble in the cell membrane. Also, the affinity of BMP7 for its low-affinity
type I receptor ECD increases 5-fold in the presence of its type II receptor
ECD. Taken together, our results provide a view of the ligand-mediated
cooperative assembly of BMP and activin receptors that does not rely on
receptor-receptor contacts.
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Figure 1.
Figure 1. The Structure of the BMP7/ActRII-ECD Complex(A
and B) Ribbon diagrams of the BMP7/ActRII-ECD complex (A) with
the 2-fold symmetry axis vertical and the membrane facing side
at the bottom and (B) the view from above (BMP7, gold and rust;
ActRII-ECD, green; cystine sulfurs, yellow space-filling).(C)
Stereo view of the interface between BMP7 and ActRII in an
orientation close to (A). The residues within 4 Å of the
binding partner as well as Glu29 are displayed as balls and
sticks. Glu29 and those residues whose mutations are known to
affect binding (pink, Figure 2) are labeled.In (A)–(C)
significant conformational changes are highlighted (dark blue),
and in (C) they are overlaid with the unbound conformations
(light blue). This figure was made using MOLSCRIPT (Kraulis,
1991).
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Figure 3.
Figure 3. The Model of the BMP7/ActRII/BMPRIa Six-Chain
Signaling ComplexBMPRIa (purple) was placed in the complex by
aligning the BMP2/BMPRIa structure (Kirsch et al., 2000a) with
BMP7.(A) Side view as in Figure 1A is shown as a solvent
accessible surface. The horizontal line represents the plane of
the membrane.(B) Bottom view (opposite from Figure 1B). Sugars
are in black. The C termini are marked with yellow dots and the
horizontal distances between them as projected onto the plane of
the membrane are 83 Å for type II-type II, 66 Å for
type I-type I, and 27 Å and 68 Å for type I-type II.
(A) and (B) were prepared with DINO (Philippsen, 2001).(C)
Stereo view of ActRII and TGF-βRII bound to their respective
ligands overlaid with the BMP2/BMPRIa structure. The BMP7/ActRII
complex was aligned as in (A) using the entire ligand. In order
to overlay the TGF-βRII binding site (tip of finger 2 on
TGF-β3) with BMP2, only 14 residues (86–92 and 98–104 of
BMP2) were used for the alignment (Hart et al., 2002). The color
scheme is BMP2, white; BMP7, gold; ActRII, green; TGF-β3, blue;
TGF-βRII, red; BMPRIa, purple. The receptors and their C
termini are labeled.
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2003,
11,
605-617)
copyright 2003.
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