PDBsum entry 3s2k

Signaling protein

PDB id: 3s2k

Contents

Protein chains

610 a.a.

76 a.a.

Ligands

NAG-NAG-FUC ×2

NAG-NAG ×2

NAG ×6

GOL ×2

Waters ×56

PDB id:

3s2k

Name:

Signaling protein

Title:

Structural basis of wnt signaling inhibition by dickkopf binding to lrp5/6.

Structure:

Low-density lipoprotein receptor-related protein 6. Chain: a, b. Fragment: ectodomain repeats 3, 4 unp residues 630-1246. Synonym: lrp-6. Engineered: yes. Dickkopf-related protein 1. Chain: c. Fragment: c-terminal domain, unp residues 178-266. Synonym: dickkopf-1, dkk-1, hdkk-1, sk.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: lrp6. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: dkk1, unq492/pro1008. Expression_system_taxid: 7108

Resolution:

2.80Å R-factor: 0.197 R-free: 0.251

Authors:

V.E.Ahn,M.L.-H.Chu,H.-J.Choi,D.Tran,A.Abo,W.I.Weis

Key ref:

V.E.Ahn et al. (2011). Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6. Dev Cell, 21, 862-873. PubMed id: 22000856

Date:

16-May-11 Release date: 02-Nov-11

Protein chains

O75581  (LRP6_HUMAN) -  Low-density lipoprotein receptor-related protein 6 from Homo sapiens

Seq: 1613 a.a.

Struc: 610 a.a.*

Protein chain

O94907  (DKK1_HUMAN) -  Dickkopf-related protein 1 from Homo sapiens

Seq: 266 a.a.

Struc: 76 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Dev Cell 21:862-873 (2011)

PubMed id: 22000856

Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6.

V.E.Ahn, M.L.Chu, H.J.Choi, D.Tran, A.Abo, W.I.Weis.

ABSTRACT

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.