PDBsum entry 2ltv

Protein binding/peptide

PDB id: 2ltv

Contents

Protein chains

36 a.a.

12 a.a.

PDB id:

2ltv

Name:

Protein binding/peptide

Title:

Yap ww2 in complex with a smad7 derived peptide

Structure:

Yorkie homolog. Chain: a. Fragment: ww2 domain (unp residues 230-265). Synonym: 65 kda yes-associated protein, yap65. Engineered: yes. Smad7 derived peptide. Chain: b. Fragment: unp residues 206-217. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: yap1, yap65. Expressed in: escherichia coli. Expression_system_taxid: 511693. Synthetic: yes. Organism_taxid: 9606

NMR struc:

40 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

P46937  (YAP1_HUMAN) -  Transcriptional coactivator YAP1 from Homo sapiens

Seq: 504 a.a.

Struc: 36 a.a.

Protein chain

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

Seq: 426 a.a.

Struc: 12 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

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.