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PDBsum entry 2kd3
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Protein binding
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PDB id
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2kd3
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References listed in PDB file
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Key reference
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Title
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Nmr structure of the wnt modulator protein sclerostin.
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Authors
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S.E.Weidauer,
P.Schmieder,
M.Beerbaum,
W.Schmitz,
H.Oschkinat,
T.D.Mueller.
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Ref.
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Biochem Biophys Res Commun, 2009,
380,
160-165.
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PubMed id
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Abstract
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Sclerostin has been identified as a negative regulator of bone growth. Initially
it was considered that Sclerostin performs its regulatory function via acting as
a modulator of bone morphogenetic proteins (BMPs) similar to known examples such
as Noggin, Chordin, and members of the DAN family. Recent findings, however,
show that Sclerostin interferes with the Wnt signaling pathway due to binding to
the Wnt co-receptor LRP5 thereby modulating bone growth. As Sclerostin is
exclusively produced by osteocytes located in bones, neutralization of its
bone-inhibiting functions makes it a highly interesting target for an
osteoanabolic therapeutic approach in diseases characterized by bone loss, such
as osteoporosis. Despite the huge interest in Sclerostin inhibitors the
molecular basis of its function and its interaction with components of the Wnt
signaling cascade has remained unclear. Here, we present the NMR structure of
murine Sclerostin providing the first insights how Sclerostin might bind to LRP5.
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