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PDBsum entry 3soq
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Protein binding/antagonist
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PDB id
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3soq
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PDB id:
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| Name: |
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Protein binding/antagonist
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Title:
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The structure of the first ywtd beta propeller domain of lrp6 in complex with a dkk1 peptide
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Structure:
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Low-density lipoprotein receptor-related protein 6. Chain: a. Fragment: unp residues 20-335. Synonym: lrp-6. Engineered: yes. Dickkopf-related protein 1. Chain: z. Fragment: unp residues 38-44. Synonym: dickkopf-1, dkk-1, hdkk-1, sk.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: lrp6. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic: yes. Organism_taxid: 9606
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Resolution:
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1.90Å
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R-factor:
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0.179
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R-free:
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0.221
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Authors:
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W.Wang,E.Bourhis,Y.Zhang,L.Rouge,Y.Wu,Y.Franke,A.G.Cochran
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Key ref:
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E.Bourhis
et al.
(2011).
Wnt antagonists bind through a short peptide to the first β-propeller domain of LRP5/6.
Structure,
19,
1433-1442.
PubMed id:
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Date:
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30-Jun-11
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Release date:
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21-Sep-11
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PROCHECK
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Headers
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References
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O75581
(LRP6_HUMAN) -
Low-density lipoprotein receptor-related protein 6 from Homo sapiens
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Seq:
Struc:
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1613 a.a.
305 a.a.
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Key: |
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Secondary structure |
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CATH domain |
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Structure
19:1433-1442
(2011)
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PubMed id:
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Wnt antagonists bind through a short peptide to the first β-propeller domain of LRP5/6.
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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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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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