5C4V: Ski-like Protein

TGF-beta signaling regulates cellular processes such as proliferation, differentiation and apoptosis through activation of SMAD transcription factors that are in turn modulated by members of the Ski-SnoN family. In this process, Ski has been shown to negatively modulate TGF-beta signaling by disrupting active R-SMAD/Co-SMAD heteromers. Here, we show that the related regulator SnoN forms a stable complex with the R-SMAD (SMAD3) and the Co-SMAD (SMAD4). To rationalize this stabilization at the molecular level, we determined the crystal structure of a complex between the SAND domain of SnoN and the MH2-domain of SMAD4. This structure shows a binding mode that is compatible with simultaneous coordination of R-SMADs. Our results show that SnoN, and SMAD heteromers can form a joint structural core for the binding of other transcription modulators. The results are of fundamental importance for our understanding of the molecular mechanisms behind the modulation of TGF-beta signaling.
PDB ID: 5C4VDownload
MMDB ID: 143904
PDB Deposition Date: 2015/6/18
Updated in MMDB: 2016/10
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
Similar Structures:
Biological Unit for 5C4V: dimeric; determined by author
Molecular Components in 5C4V
Label Count Molecule
Proteins (2 molecules)
Mothers Against Decapentaplegic Homolog 4(Gene symbol: SMAD4)
Molecule annotation
Ski-like Protein(Gene symbol: SKIL)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB