PDBsum entry 2djy

Ligase/signaling protein

PDB id: 2djy

Contents

Protein chains

42 a.a. *

20 a.a. *

* Residue conservation analysis

PDB id:

2djy

Name:

Ligase/signaling protein

Title:

Solution structure of smurf2 ww3 domain-smad7 py peptide complex

Structure:

Smad ubiquitination regulatory factor 2. Chain: a. Fragment: ww3 domain. Synonym: ubiquitin--protein ligase smurf2, smad-specific e3 ubiquitin ligase 2, hsmurf2. Engineered: yes. Mothers against decapentaplegic homolog 7. Chain: b. Fragment: py motif region.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: smurf2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: smad7, madh7, madh8.

NMR struc:

30 models

Authors:

P.A.Chong,H Lin,J.L.Wrana,J.D.Forman-Kay

Key ref:

P.A.Chong et al. (2006). An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2. J Biol Chem, 281, 17069-17075. PubMed id: 16641086 DOI: 10.1074/jbc.M601493200

Date:

06-Apr-06 Release date: 02-May-06

Protein chain

Q9HAU4  (SMUF2_HUMAN) -  E3 ubiquitin-protein ligase SMURF2 from Homo sapiens

Seq: 748 a.a.

Struc: 42 a.a.*

Protein chain

O15105  (SMAD7_HUMAN) -  Mothers against decapentaplegic homolog 7 from Homo sapiens

Seq: 426 a.a.

Struc: 20 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chain A: E.C.2.3.2.26 - HECT-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
• Enzyme class 2: Chain B: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1074/jbc.M601493200

J Biol Chem 281:17069-17075 (2006)

PubMed id: 16641086

An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2.

P.A.Chong, H.Lin, J.L.Wrana, J.D.Forman-Kay.

ABSTRACT

Smurf2 is an E3 ubiquitin ligase that drives degradation of the transforming growth factor-beta receptors and other targets. Recognition of the receptors by Smurf2 is accomplished through an intermediary protein, Smad7. Here we have demonstrated that the WW3 domain of Smurf2 can directly bind to the Smad7 polyproline-tyrosine (PY) motif. Of particular interest, the highly conserved WW domain binding site Trp, which interacts with target PY motifs, is a Phe in the Smurf2 WW3 domain. To examine this interaction, the solution structure of the complex between the Smad7 PY motif region (ELESPPPPYSRYPMD) and the Smurf2 WW3 domain was determined. The structure reveals that, in addition to binding the PY motif, the WW3 domain binds six residues C-terminal to the PY motif (PY-tail). Although the Phe in the WW3 domain binding site decreases affinity relative to the canonical Trp, this is balanced by additional interactions between the PY-tail and the beta1-strand and beta1-beta2 loop of the WW3 domain. The interaction between the Smurf2 WW3 domain and the Smad7 PY motif is the first example of PY motif recognition by a WW domain with a Phe substituted for the binding site Trp. This unusual interaction allows the Smurf2 WW3 domain to recognize a subset of PY motif-containing proteins utilizing an expanded surface to provide specificity.

Selected figure(s)

Figure 1.
FIGURE 1. Solution structure of the Smurf2 WW3 domain-Smad7 PY peptide complex. a, superposition of the 30 lowest energy structures. The WW3 domain backbone is shown in blue and side chains in turquoise, except for positions typically occupied by conserved Trp residues, which are in green. The PY peptide backbone is red with side chains shown in gold. b, ribbon diagram of the lowest energy structure. The coloring scheme is as in a, except that WW3 domain loop regions are shown in gray. Residues designated with a prime symbol (') are Smad7 residues. For clarity, some side chains are not shown. Figs. 1, 2, 3a, and 5b were generated using MOLMOL (37). N, N terminus; C, C terminus.

Figure 2.
FIGURE 2. Superposition of the PY motifs and binding pockets from the Smad7-Smurf2 WW3 domain complex and the -dystroglycan-dystrophin WW domain complex. Smad7 and Smurf2 are shown in red and blue and -dystroglycan and dystrophin in black and gray, respectively. Labels in parentheses indicate residues from the -dystroglycan-dystrophin complex.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 17069-17075) copyright 2006.

Figures were selected by an automated process.