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PDBsum entry 3s2k
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Signaling protein
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PDB id
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3s2k
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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 wnt signaling inhibition by dickkopf binding to lrp5/6.
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Authors
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V.E.Ahn,
M.L.Chu,
H.J.Choi,
D.Tran,
A.Abo,
W.I.Weis.
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Ref.
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Dev Cell, 2011,
21,
862-873.
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PubMed id
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Abstract
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LDL receptor-related proteins 5 and 6 (LRP5/6) are coreceptors for Wnt growth
factors, and also bind Dkk proteins, secreted inhibitors of Wnt signaling. The
LRP5/6 ectodomain contains four β-propeller/EGF-like domain repeats. The first
two repeats, LRP6(1-2), bind to several Wnt variants, whereas LRP6(3-4) binds
other Wnts. We present the crystal structure of the Dkk1 C-terminal domain bound
to LRP6(3-4), and show that the Dkk1 N-terminal domain binds to LRP6(1-2),
demonstrating that a single Dkk1 molecule can bind to both portions of the LRP6
ectodomain and thereby inhibit different Wnts. Small-angle X-ray scattering
analysis of LRP6(1-4) bound to a noninhibitory antibody fragment or to
full-length Dkk1 shows that in both cases the ectodomain adopts a curved
conformation that places the first three repeats at a similar height relative to
the membrane. Thus, Wnts bound to either portion of the LRP6 ectodomain likely
bear a similar spatial relationship to Frizzled coreceptors.
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