1U7V

Crystal Structure of the phosphorylated Smad2/Smad4 heterotrimeric complex

Summary for 1U7V

• Entry DOI: 10.2210/pdb1u7v/pdb
• Related: 1U7F
• Descriptor: Mothers against decapentaplegic homolog 2, Mothers against decapentaplegic homolog 4 (2 entities in total)
• Functional Keywords: smad, tgf-beta, signal transduction, protein complex, phosphorylation, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q15796 Q13485
• Total number of polymer chains: 3
• Total formula weight: 70734.00

Authors

Chacko, B.M.,Qin, B.Y.,Tiwari, A.,Shi, G.,Lam, S.,Hayward, L.J.,de Caestecker, M.,Lin, K. (deposition date: 2004-08-04, release date: 2004-09-28, Last modification date: 2024-10-16)

Primary citation

Chacko, B.M.,Qin, B.Y.,Tiwari, A.,Shi, G.,Lam, S.,Hayward, L.J.,De Caestecker, M.,Lin, K.
Structural basis of heteromeric smad protein assembly in tgf-Beta signaling
Mol.Cell, 15:813-823, 2004

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.

PubMed: 15350224
DOI: 10.1016/j.molcel.2004.07.016

Experimental method

X-RAY DIFFRACTION (2.7 Å)