Structural basis of Smad2 recognition by the Smad anchor for receptor activation.
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Wu G, Chen YG, Ozdamar B, Gyuricza CA, Chong PA, Wrana JL, Massague J, Shi Y
Structural basis of Smad2 recognition by the Smad anchor for receptor activation.
Science. 2000 Jan 7;287(5450):92-7.
- PubMed ID
- 10615055 [ View in PubMed]
- Abstract
The Smad proteins mediate transforming growth factor-beta (TGFbeta) signaling from the transmembrane serine-threonine receptor kinases to the nucleus. The Smad anchor for receptor activation (SARA) recruits Smad2 to the TGFbeta receptors for phosphorylation. The crystal structure of a Smad2 MH2 domain in complex with the Smad-binding domain (SBD) of SARA has been determined at 2.2 angstrom resolution. SARA SBD, in an extended conformation comprising a rigid coil, an alpha helix, and a beta strand, interacts with the beta sheet and the three-helix bundle of Smad2. Recognition between the SARA rigid coil and the Smad2 beta sheet is essential for specificity, whereas interactions between the SARA beta strand and the Smad2 three-helix bundle contribute significantly to binding affinity. Comparison of the structures between Smad2 and a comediator Smad suggests a model for how receptor-regulated Smads are recognized by the type I receptors.