4C8V: Xenopus Rspo2 Fu1-fu2 Crystal Form I

The four R-spondin (Rspo) proteins are secreted agonists of Wnt signalling in vertebrates, functioning in embryogenesis and adult stem cell biology. Through ubiquitination and degradation of Wnt receptors, the transmembrane E3 ubiquitin ligase ZNRF3 and related RNF43 antagonize Wnt signalling. Rspo ligands have been reported to inhibit the ligase activity through direct interaction with ZNRF3 and RNF43. Here we report multiple crystal structures of the ZNRF3 ectodomain (ZNRF3ecto), a signalling-competent Furin1-Furin2 (Fu1-Fu2) fragment of Rspo2 (Rspo2Fu1-Fu2), and Rspo2Fu1-Fu2 in complex with ZNRF3ecto, or RNF43ecto. A prominent loop in Fu1 clamps into equivalent grooves in the ZNRF3ecto and RNF43ecto surface. Rspo binding enhances dimerization of ZNRF3ecto but not of RNF43ecto. Comparison of the four Rspo proteins, mutants and chimeras in biophysical and cellular assays shows that their signalling potency depends on their ability to recruit ZNRF3 or RNF43 via Fu1 into a complex with LGR receptors, which interact with Rspo via Fu2.
PDB ID: 4C8VDownload
MMDB ID: 115246
PDB Deposition Date: 2013/10/1
Updated in MMDB: 2013/11
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 4C8V: monomeric; determined by author and by software (PQS)
Molecular Components in 4C8V
Label Count Molecule
Protein (1 molecule)
R-spondin-2(Gene symbol: rspo2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB