Structural Mechanism of Smad4 Recognition by the Nuclear Oncoprotein Ski
Copyright policy )Structural Mechanism of Smad4 Recognition by the Nuclear Oncoprotein Ski
The Ski family of nuclear oncoproteins represses TGF-beta signaling through interactions with the Smad proteins. The crystal structure of the Smad4 binding domain of human c-Ski in complex with the MH2 domain of Smad4 reveals specific recognition of the Smad4 L3 loop region by a highly conserved interaction loop (I loop) from Ski. The Ski binding surface on Smad4 significantly overlaps with that required for binding of the R-Smads. Indeed, Ski disrupts the formation of a functional complex between the Co- and R-Smads, explaining how it could lead to repression of TGF-beta, activin, and BMP responses. Intriguingly, the structure of the Ski fragment, stabilized by a bound zinc atom, resembles the SAND domain, in which the corresponding I loop is responsible for DNA binding.
- Lawrence Berkeley National Laboratory United States
- University of California, Berkeley United States
- PRINCETON UNIVERSITY
- College of New Jersey United States
- UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
Models, Molecular, Biochemistry, Genetics and Molecular Biology(all), Molecular Sequence Data, Nuclear Proteins, Protein Structure, Tertiary, DNA-Binding Proteins, Mutagenesis, Transforming Growth Factor beta, Proto-Oncogene Proteins, Trans-Activators, Tumor Cells, Cultured, Humans, Amino Acid Sequence, Cell Line, Transformed, Signal Transduction, Smad4 Protein
Models, Molecular, Biochemistry, Genetics and Molecular Biology(all), Molecular Sequence Data, Nuclear Proteins, Protein Structure, Tertiary, DNA-Binding Proteins, Mutagenesis, Transforming Growth Factor beta, Proto-Oncogene Proteins, Trans-Activators, Tumor Cells, Cultured, Humans, Amino Acid Sequence, Cell Line, Transformed, Signal Transduction, Smad4 Protein
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).191 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!