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PDBsum entry 2ltz
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Protein binding/peptide
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PDB id
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2ltz
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References listed in PDB file
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Key reference
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Title
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Structural basis for the versatile interactions of smad7 with regulator ww domains in tgf-β Pathways.
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Authors
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E.Aragón,
N.Goerner,
Q.Xi,
T.Gomes,
S.Gao,
J.Massagué,
M.J.Macias.
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Ref.
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Structure, 2012,
20,
1726-1736.
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PubMed id
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Abstract
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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.
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