PDBsum entry 4li2

Hormone receptor/signaling protein

PDB id: 4li2

Contents

Protein chains

422 a.a.

103 a.a.

PDB id:

4li2

Name:

Hormone receptor/signaling protein

Title:

Crystal structures of lgr4 and its complex with r-spondin1

Structure:

Leucine-rich repeat-containing g-protein coupled receptor 4. Chain: a. Fragment: extracellular domain residues 23-454. Engineered: yes. Mutation: yes. R-spondin-1. Chain: b. Fragment: fu 1 and fu 2 repeat residues 33-144.

Source:

Xenopus (silurana) tropicalis. Western clawed frog. Organism_taxid: 8364. Gene: lgr4. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293 cells. Homo sapiens. Human.

Resolution:

3.19Å R-factor: 0.235 R-free: 0.284

Authors:

Y.Xu,K.Rajashankar,D.Robev

Key ref:

K.Xu et al. (2013). Crystal structures of Lgr4 and its complex with R-spondin1. Structure, 21, 1683-1689. PubMed id: 23891289 DOI: 10.1016/j.str.2013.07.001

Date:

02-Jul-13 Release date: 07-Aug-13

Protein chain

B0BLW3  (LGR4_XENTR) -  Leucine-rich repeat-containing G-protein coupled receptor 4 from Xenopus tropicalis

Seq: 955 a.a.

Struc: 422 a.a.*

Protein chain

Q2MKA7  (RSPO1_HUMAN) -  R-spondin-1 from Homo sapiens

Seq: 263 a.a.

Struc: 103 a.a.

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

DOI no: 10.1016/j.str.2013.07.001

Structure 21:1683-1689 (2013)

PubMed id: 23891289

Crystal structures of Lgr4 and its complex with R-spondin1.

K.Xu, Y.Xu, K.R.Rajashankar, D.Robev, D.B.Nikolov.

ABSTRACT

The leucine-rich repeat-containing G-protein-coupled receptors (Lgrs) are a large membrane protein family mediating signaling events during development and in the adult organism. Type 2 Lgrs, including Lgr4, Lgr5, and Lgr6, play crucial roles in embryonic development and in several cancers. They also regulate adult stem cell maintenance via direct association with proteins in the Wnt signaling pathways, including Lrp5/6 and frizzled receptors. The R-spondins (Rspo) were recently identified as functional ligands for type 2 Lgrs and were shown to synergize with both canonical and noncanonical Wnt signaling pathways. We determined and report the structure of the Lgr4 ectodomain alone and bound to Rspo1. The structures reveal an extended horseshoe leucine-rich repeat (LRR) receptor architecture that binds, with its concave side, the ligand furin-like repeats via an intimate interface. The molecular details of ligand/receptor recognition provide insight into receptor activation and could serve as template for stem-cell-based regenerative therapeutics development.