PDBsum entry 4c9a

Ligase

PDB id

4c9a

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Contents

			Protein chains

					153 a.a.


					103 a.a.

PDB id:

4c9a

Links

Name:

Ligase

Title:

Mouse znrf3 ectodomain in complex with xenopus rspo2 fu1-fu2 (seleno met) crystal form i

Structure:

E3 ubiquitin-protein ligase znrf3. Chain: a, c. Fragment: ectodomain, residues 1-165. Synonym: zinc/ring finger protein 3. Engineered: yes. R-spondin-2. Chain: b, d. Fragment: fu1-fu2, residues 32-152. Synonym: roof plate-specific spondin-2, rspo2.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t. Xenopus (silurana) tropicalis. Western clawed frog. Organism_taxid: 8364.

Resolution:

2.40Å

R-factor:

0.199

R-free:

0.273

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:

02-Oct-13

Release date:

20-Nov-13

PROCHECK

	Headers

	References

Protein chains

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

Seq: Struc:

Seq: Struc:					913 a.a. 153 a.a.

Protein chains

Q5M7L6 (RSPO2_XENTR) - R-spondin-2 from Xenopus tropicalis

Seq: Struc:					243 a.a. 103 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

Chains A, C: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

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.