Structural basis of heteromeric smad protein assembly in TGF-beta signaling
Graduate School of Biomedical Sciences; Department of Neurology; Department of Biochemistry and Molecular Pharmacology
Life Sciences | Medicine and Health Sciences
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
Mol Cell. 2004 Sep 10;15(5):813-23. Link to article on publisher's site
Chacko BM, Qin BY, Tiwari A, Shi G, Lam SS, Hayward LJ, De Caestecker M, Lin K. (2004). Structural basis of heteromeric smad protein assembly in TGF-beta signaling. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1016/j.molcel.2004.07.016. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/193