GSBS Student Publications
Title
Structural basis of heteromeric smad protein assembly in TGF-beta signaling
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Neurology; Department of Biochemistry and Molecular Pharmacology
Date
9-8-2004
Document Type
Article
Medical Subject Headings
Animals; 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
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
The 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.
Rights and Permissions
Citation: Mol Cell. 2004 Sep 10;15(5):813-23. Link to article on publisher's site
DOI of Published Version
10.1016/j.molcel.2004.07.016
Related Resources
Journal Title
Molecular cell
PubMed ID
15350224
Repository Citation
Chacko, Benoy Maramparambil; Qin, Bin Y.; Tiwari, Ashutosh; Shi, Genbin; Lam, Suvana S.; Hayward, Lawrence J.; De Caestecker, Mark; and Lin, Kai, "Structural basis of heteromeric smad protein assembly in TGF-beta signaling" (2004). GSBS Student Publications. 193.
https://escholarship.umassmed.edu/gsbs_sp/193