2LTW: YAP WW1 in complex with a Smad7 derived peptide

Transforming growth factor (TGF)-beta 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-beta 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-beta and BMP pathways.
PDB ID: 2LTWDownload
MMDB ID: 105119
PDB Deposition Date: 2012/6/4
Updated in MMDB: 2012/11
Experimental Method:
solution nmr
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 2LTW: dimeric; determined by author
Molecular Components in 2LTW
Label Count Molecule
Proteins (2 molecules)
Yorkie Homolog(Gene symbol: YAP1)
Molecule annotation
Smad7 Derived Peptide(Gene symbol: SMAD7)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB