5C4V

SnoN Stabilizes the SMAD3/SMAD4 Protein Complex.

(2017) Sci Rep 7: 46370-46370

• PubMed: 28397834 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1038/srep46370
• Primary Citation of Related Structures:  
  5C4V


• PubMed Abstract: 
  

  TGF-β 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-β 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-β signaling.

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Organizational Affiliation: 

Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.