Structural basis of heteromeric Smad protein assembly in TGF-β signaling

被引：167

作者：

Chacko, BM

Qin, BY

Tiwari, A

Shi, GB

Lam, S

Hayward, LJ

de Caestecker, M

Lin, K ^{[1
]}

机构：

[1] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01655 USA

[2] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA

[3] Vanderbilt Univ, Med Ctr, Dept Nephrol, Nashville, TN 37232 USA

来源：

MOLECULAR CELL | 2004年 / 15卷 / 05期

关键词：

D O I：

10.1016/j.molcel.2004.07.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 Angstrom, and Smad2/Smad4 to 2.7 Angstrom 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.

引用

页码：813 / 823

页数：11

共 44 条

[1] T beta RI phosphorylation of Smad2 on Ser(465) and Ser(467) is required for Smad2-Smad4 complex formation and signaling [J].