Structural basis of heteromeric smad protein assembly in TGF-beta signaling
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AuthorsChacko, Benoy Maramparambil
Qin, Bin Y.
Lam, Suvana S.
Hayward, Lawrence J.
De Caestecker, Mark
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Department of Neurology
Graduate School of Biomedical Sciences
Document TypeJournal Article
KeywordsAnimals; COS Cells; Crystallography, X-Ray; DNA-Binding Proteins; Heat; Macromolecular Substances; Models, Molecular; Molecular Conformation; Phosphorylation; Polymers; Protein Structure, Tertiary; Protein Subunits; Signal Transduction; Smad2 Protein; Smad3 Protein; Temperature; Trans-Activators; Transforming Growth Factor beta; Tumor Markers, Biological
Medicine and Health Sciences
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AbstractThe formation of protein complexes between phosphorylated R-Smads and Smad4 is a central event in the TGF-beta signaling pathway. We have determined the crystal structure of two R-Smad/Smad4 complexes, Smad3/Smad4 to 2.5 angstroms, and Smad2/Smad4 to 2.7 angstroms. Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. Preferential formation of the R-Smad/Smad4 heterotrimer over the R-Smad homotrimer is largely enthalpy driven, contributed by the unique presence of strong electrostatic interactions within the heterotrimeric interfaces. The study supports a common mechanism of Smad protein assembly in TGF-beta superfamily signaling.
SourceMol Cell. 2004 Sep 10;15(5):813-23. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/33403
Related ResourcesLink to article in PubMed
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