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

Related Resources

Link to article in PubMed

Journal Title

Molecular cell

PubMed ID

15350224