PDBsum entry 4wip

Signaling protein

PDB id: 4wip

Contents

Protein chains

81 a.a.

Ligands

1PE ×3

Waters ×13

PDB id:

4wip

Name:

Signaling protein

Title:

Dix domain of human dvl2

Structure:

Segment polarity protein dishevelled homolog dvl-2. Chain: a, b, c. Fragment: unp residues 13-105. Synonym: dishevelled-2,dsh homolog 2. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dvl2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.69Å R-factor: 0.224 R-free: 0.248

Authors:

M.Fiedler,M.Bienz,J.Madrzak,J.W.Chin

Key ref:

J.Madrzak et al. (2015). Ubiquitination of the Dishevelled DIX domain blocks its head-to-tail polymerization. Nat Commun, 6, 6718. PubMed id: 25907794 DOI: 10.1038/ncomms7718

Date:

26-Sep-14 Release date: 13-May-15

Protein chains

O14641  (DVL2_HUMAN) -  Segment polarity protein dishevelled homolog DVL-2 from Homo sapiens

Seq: 736 a.a.

Struc: 81 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/ncomms7718

Nat Commun 6:6718 (2015)

PubMed id: 25907794

Ubiquitination of the Dishevelled DIX domain blocks its head-to-tail polymerization.

J.Madrzak, M.Fiedler, C.M.Johnson, R.Ewan, A.Knebel, M.Bienz, J.W.Chin.

ABSTRACT

Dishevelled relays Wnt signals from the plasma membrane to different cytoplasmic effectors. Its signalling activity depends on its DIX domain, which undergoes head-to-tail polymerization to assemble signalosomes. The DIX domain is ubiquitinated in vivo at multiple lysines, which can be antagonized by various deubiquitinases (DUBs) including the CYLD tumour suppressor that attenuates Wnt signalling. Here, we generate milligram quantities of pure human Dvl2 DIX domain mono-ubiquitinated at two lysines (K54 and K58) by genetically encoded orthogonal protection with activated ligation (GOPAL), to investigate their effect on DIX polymerization. We show that the ubiquitination of DIX at K54 blocks its polymerization in solution, whereas DIX58-Ub remains oligomerization-competent. DUB profiling identified 28 DUBs that cleave DIX-ubiquitin conjugates, half of which prefer, or are specific for, DIX54-Ub, including Cezanne and CYLD. These DUBs thus have the potential to promote Dvl polymerization and signalosome formation, rather than antagonize it as previously thought for CYLD.