PDBsum entry 2ltz

Protein binding/peptide

PDB id: 2ltz

Contents

Protein chains

37 a.a.

15 a.a.

PDB id:

2ltz

Name:

Protein binding/peptide

Title:

Smurf2 ww3 domain in complex with a smad7 derived peptide

Structure:

E3 ubiquitin-protein ligase smurf2. Chain: a. Fragment: ww3 domain (unp residues 297-333). Synonym: hsmurf2, smad ubiquitination regulatory factor 2, smad- specific e3 ubiquitin-protein ligase 2. Engineered: yes. Smad7 derived peptide. Chain: b. Fragment: unp residues 203-217.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: smurf2. Expressed in: escherichia coli. Expression_system_taxid: 511693. Synthetic: yes. Organism_taxid: 9606

NMR struc:

20 models

Authors:

M.J.Macias,E.Aragon,N.Goerner,Q.Xi,T.Lopes,S.Gao,J.Massague

Key ref:

E.Aragón et al. (2012). Structural basis for the versatile interactions of Smad7 with regulator WW domains in TGF-β Pathways. Structure, 20, 1726-1736. PubMed id: 22921829

Date:

04-Jun-12 Release date: 21-Nov-12

Protein chain

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

Seq: 748 a.a.

Struc: 37 a.a.

Protein chain

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

Seq: 426 a.a.

Struc: 15 a.a.

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.

Structure 20:1726-1736 (2012)

PubMed id: 22921829

Structural basis for the versatile interactions of Smad7 with regulator WW domains in TGF-β Pathways.

E.Aragón, N.Goerner, Q.Xi, T.Gomes, S.Gao, J.Massagué, M.J.Macias.

ABSTRACT

Transforming growth factor (TGF)-β and BMP signaling is mediated by Smads 1-5 (R-Smads and Co-Smads) and inhibited by Smad7, a major hub of regulation of TGF-β and BMP receptors by negative feedback and antagonistic signals. The transcription coactivator YAP and the E3 ubiquitin ligases Smurf1/2 and Nedd4L target R-Smads for activation or degradation, respectively. Pairs of WW domain in these regulators bind PY motifs and adjacent CDK/MAPK and GSK3 phosphorylation sites in R-Smads in a selective and regulated manner. In contrast, here we show that Smad7 binds YAP, Smurf1, Smurf2, and Nedd4L constitutively, the binding involving a PY motif in Smad7 and no phosphorylation. We also provide a structural basis for how regulators that use WW domain pairs for selective interactions with R-Smads, resort to one single versatile WW domain for binding Smad7 to centralize regulation in the TGF-β and BMP pathways.