PDBsum entry 4c8f

Ligase

PDB id: 4c8f

Contents

Protein chains

137 a.a.

PDB id:

4c8f

Name:

Ligase

Title:

Mouse znrf3 ectodomain crystal form iv

Structure:

E3 ubiquitin-protein ligase znrf3. Chain: a, b, c, d. Fragment: ectodomain, residues 53-205. Synonym: zinc/ring finger protein 3, znrf3. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t.

Resolution:

2.69Å R-factor: 0.240 R-free: 0.341

Authors:

M.Zebisch,E.Y.Jones

Key ref:

M.Zebisch et al. (2013). Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist R-spondin. Nat Commun, 4, 2787. PubMed id: 24225776 DOI: 10.1038/ncomms3787

Date:

30-Sep-13 Release date: 20-Nov-13

Protein chains

Q5SSZ7  (ZNRF3_MOUSE) -  E3 ubiquitin-protein ligase ZNRF3 from Mus musculus

Seq: 913 a.a.

Struc: 137 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine

DOI no: 10.1038/ncomms3787

Nat Commun 4:2787 (2013)

PubMed id: 24225776

Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist R-spondin.

M.Zebisch, Y.Xu, C.Krastev, B.T.MacDonald, M.Chen, R.J.Gilbert, X.He, E.Y.Jones.

ABSTRACT

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.