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PDBsum entry 3s94

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protein ligands links
Signaling protein PDB id
3s94
Jmol PyMol
Contents
Protein chain
587 a.a.
Ligands
NAG-NAG ×2
NAG
PDB id:
3s94
Name: Signaling protein
Title: Crystal structure of lrp6-e1e2
Structure: Low-density lipoprotein receptor-related protein chain: a, b. Fragment: e1e2, residues 20-630. Synonym: lrp-6. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: lrp6. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.80Å     R-factor:   0.240     R-free:   0.296
Authors: Z.Cheng,W.Xu
Key ref: Z.Cheng et al. (2011). Crystal structures of the extracellular domain of LRP6 and its complex with DKK1. Nat Struct Mol Biol, 18, 1204-1210. PubMed id: 21984209
Date:
31-May-11     Release date:   02-Nov-11    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
O75581  (LRP6_HUMAN) -  Low-density lipoprotein receptor-related protein 6
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1613 a.a.
587 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
Nat Struct Mol Biol 18:1204-1210 (2011)
PubMed id: 21984209  
 
 
Crystal structures of the extracellular domain of LRP6 and its complex with DKK1.
Z.Cheng, T.Biechele, Z.Wei, S.Morrone, R.T.Moon, L.Wang, W.Xu.
 
  ABSTRACT  
 
Low-density-lipoprotein (LDL) receptor-related proteins 5 and 6 (LRP5/6) are Wnt co-receptors essential for Wnt/β-catenin signaling. Dickkopf 1 (DKK1) inhibits Wnt signaling by interacting with the extracellular domains of LRP5/6 and is a drug target for multiple diseases. Here we present the crystal structures of a human LRP6-E3E4-DKK1 complex and the first and second halves of human LRP6's four propeller-epidermal growth factor (EGF) pairs (LRP6-E1E2 and LRP6-E3E4). Combined with EM analysis, these data demonstrate that LRP6-E1E2 and LRP6-E3E4 form two rigid structural blocks, with a short intervening hinge that restrains their relative orientation. The C-terminal domain of DKK1 (DKK1c) interacts with the top surface of the LRP6-E3 YWTD propeller and given their structural similarity, probably also that of the LRP6-E1 propeller, through conserved hydrophobic patches buttressed by a network of salt bridges and hydrogen bonds. Our work provides key insights for understanding LRP5/6 structure and the interaction of LRP5/6 with DKK, as well as for drug discovery.
 

 

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