Download MendeleyStructural basis of heteromeric smad protein assembly in tgf-Beta signaling
Chacko, B.M., Qin, B.Y., Tiwari, A., Shi, G., Lam, S., Hayward, L.J., De Caestecker, M., Lin, K.(2004) Mol Cell 15: 813-823
- PubMed: 15350224
- DOI: https://doi.org/10.1016/j.molcel.2004.07.016
- Primary Citation of Related Structures:
1U7F, 1U7V - PubMed 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.
Organizational Affiliation:
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
