2LTX

Smurf1 WW2 domain in complex with a Smad7 derived peptide

Summary for 2LTX

• Entry DOI: 10.2210/pdb2ltx/pdb
• Related: 2LTV 2LTW 2LTY 2LTZ
• NMR Information: BMRB: 18500
• Descriptor: E3 ubiquitin-protein ligase SMURF1, Smad7 derived peptide (2 entities in total)
• Functional Keywords: ww, smurf1, smad7, protein binding-peptide complex, protein binding/peptide
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q9HCE7; Nucleus: O15105
• Total number of polymer chains: 2
• Total formula weight: 5836.44

Authors

Macias, M.J.,Aragon, E.,Goerner, N.,Xi, Q.,Lopes, T.,Gao, S.,Massague, J. (deposition date: 2012-06-04, release date: 2012-11-21, Last modification date: 2024-05-01)

Primary citation

Aragon, E.,Goerner, N.,Xi, Q.,Gomes, T.,Gao, S.,Massague, J.,Macias, M.J.
Structural Basis for the Versatile Interactions of Smad7 with Regulator WW Domains in TGF-beta Pathways.
Structure, 20:1726-1736, 2012

PubMed 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.

PubMed: 22921829
DOI: 10.1016/j.str.2012.07.014

Experimental method

SOLUTION NMR