PDBsum entry 4bsr

Signaling protein

PDB id: 4bsr

Contents

Protein chains

483 a.a.

103 a.a.

Ligands

NAG-NAG-BMA

NAG-NAG ×3

NAG

PDB id:

4bsr

Name:

Signaling protein

Title:

Structure of the ectodomain of lgr5 in complex with r-spondin-1 (fu1fu2) in p22121 crystal form

Structure:

Leucine-rich repeat-containing g-protein coupled receptor 5. Chain: a, b. Fragment: extracellular lrr domain, residues 22-543. Synonym: g-protein coupled receptor 49, g-protein coupled receptor 67, g-protein coupled receptor hg38. Engineered: yes. Other_details: n-linked glycosylations at asn 63,77,208,500. R-spondin-1.

Source:

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

Resolution:

3.20Å R-factor: 0.232 R-free: 0.258

Authors:

W.C.Peng,W.De Lau,F.Forneris,J.C.M.Granneman,M.Huch,H.Clevers,P.Gros

Key ref:

W.C.Peng et al. (2013). Structure of stem cell growth factor R-spondin 1 in complex with the ectodomain of its receptor LGR5. Cell Rep, 3, 1885-1892. PubMed id: 23809763 DOI: 10.1016/j.celrep.2013.06.009

Date:

11-Jun-13 Release date: 19-Jun-13

Protein chains

O75473  (LGR5_HUMAN) -  Leucine-rich repeat-containing G-protein coupled receptor 5 from Homo sapiens

Seq: 907 a.a.

Struc: 483 a.a.

Protein chains

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

Seq: 263 a.a.

Struc: 103 a.a.

DOI no: 10.1016/j.celrep.2013.06.009

Cell Rep 3:1885-1892 (2013)

PubMed id: 23809763

Structure of stem cell growth factor R-spondin 1 in complex with the ectodomain of its receptor LGR5.

W.C.Peng, W.de Lau, F.Forneris, J.C.Granneman, M.Huch, H.Clevers, P.Gros.

ABSTRACT

Leucine-rich repeat-containing G protein-coupled receptors 4-6 (LGR4-LGR6) are receptors for R-spondins, potent Wnt agonists that exert profound trophic effects on Wnt-driven stem cells compartments. We present crystal structures of a signaling-competent fragment of R-spondin 1 (Rspo1) at a resolution of 2.0 Å and its complex with the LGR5 ectodomain at a resolution of 3.2 Å. Ecto-LGR5 binds Rspo1 at its concave leucine-rich-repeat (LRR) surface, forming a dimeric 2:2 complex. Fully conserved residues on LGR4-LGR6 explain promiscuous binding of R-spondins. A phenylalanine clamp formed by Rspo1 Phe106 and Phe110 pinches Ala190 of LGR5 and is critical for binding. Mutations related to congenital anonychia reduce signaling, but not binding of Rspo1 to LGR5. Furthermore, antibody binding to the extended loop of the C-terminal LRR cap of LGR5 activates signaling in a ligand-independent manner. Thus, our data reveal binding of R-spondins to conserved sites on LGR4-LGR6 and, in analogy to FSHR and related receptors, suggest a direct signaling role for LGR4-LGR6 in addition to its formation of Wnt receptor and coreceptor complexes.