GSBS Student Publications

Title

Structural basis of heteromeric smad protein assembly in TGF-beta signaling

GSBS Program

Biochemistry & Molecular Pharmacology

Publication Date

2004-09-08

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Neurology; Department of Biochemistry and Molecular Pharmacology

Document Type

Article

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.

DOI of Published Version

10.1016/j.molcel.2004.07.016

Source

Mol Cell. 2004 Sep 10;15(5):813-23. Link to article on publisher's site

Journal/Book/Conference Title

Molecular cell

Related Resources

Link to article in PubMed

PubMed ID

15350224

Share

COinS