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PDBsum entry 3sob
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Protein binding/immune system
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PDB id
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3sob
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Contents |
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213 a.a.
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305 a.a.
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222 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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Wnt antagonists bind through a short peptide to the first β-Propeller domain of lrp5/6.
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Authors
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E.Bourhis,
W.Wang,
C.Tam,
J.Hwang,
Y.Zhang,
D.Spittler,
O.W.Huang,
Y.Gong,
A.Estevez,
I.Zilberleyb,
L.Rouge,
C.Chiu,
Y.Wu,
M.Costa,
R.N.Hannoush,
Y.Franke,
A.G.Cochran.
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Ref.
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Structure, 2011,
19,
1433-1442.
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
91%.
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Abstract
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The Wnt pathway inhibitors DKK1 and sclerostin (SOST) are important therapeutic
targets in diseases involving bone loss or damage. It has been appreciated that
Wnt coreceptors LRP5/6 are also important, as human missense mutations that
result in bone overgrowth (bone mineral density, or BMD, mutations) cluster to
the E1 propeller domain of LRP5. Here, we report a crystal structure of LRP6 E1
bound to an antibody, revealing that the E1 domain is a peptide recognition
module. Remarkably, the consensus E1 binding sequence is a close match to a
conserved tripeptide motif present in all Wnt inhibitors that bind LRP5/6. We
show that this motif is important for DKK1 and SOST binding to LRP6 and for
inhibitory function, providing a detailed structural explanation for the effect
of the BMD mutations.
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