PDBsum entry 5fws

Signaling protein

PDB id: 5fws

Contents

Protein chain

288 a.a.

Ligands

SO4

NAG ×3

Metals

_CA

Waters ×79

PDB id:

5fws

Name:

Signaling protein

Title:

Wnt modulator kremen crystal form i at 1.90a

Structure:

Kremen protein 1. Chain: a. Fragment: ecd, residues 29-373. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293.

Resolution:

1.90Å R-factor: 0.181 R-free: 0.227

Authors:

M.Zebisch,V.A.Jackson,E.Y.Jones

Key ref:

M.Zebisch et al. (2016). Structure of the Dual-Mode Wnt Regulator Kremen1 and Insight into Ternary Complex Formation with LRP6 and Dickkopf. Structure, 24, 1599-1605. PubMed id: 27524201 DOI: 10.1016/j.str.2016.06.020

Date:

21-Feb-16 Release date: 20-Jul-16

Protein chain

Q96MU8  (KREM1_HUMAN) -  Kremen protein 1 from Homo sapiens

Seq: 473 a.a.

Struc: 288 a.a.

DOI no: 10.1016/j.str.2016.06.020

Structure 24:1599-1605 (2016)

PubMed id: 27524201

Structure of the Dual-Mode Wnt Regulator Kremen1 and Insight into Ternary Complex Formation with LRP6 and Dickkopf.

M.Zebisch, V.A.Jackson, Y.Zhao, E.Y.Jones.

ABSTRACT

Kremen 1 and 2 have been identified as co-receptors for Dickkopf (Dkk) proteins, hallmark secreted antagonists of canonical Wnt signaling. We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains. The structures reveal an unpredicted homology of the WSC domain to hepatocyte growth factor. We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD. DKK1CRD2 is sandwiched between LRP6PE3 and KRM1Kringle-WSC. Modeling studies supported by surface plasmon resonance suggest a direct interaction site between Krm1CUB and Lrp6PE2.