Structural basis of Smad2 recognition by the Smad anchor for receptor activation

G Wu, YG Chen, B Ozdamar, CA Gyuricza, PA Chong… - Science, 2000 - science.org
G Wu, YG Chen, B Ozdamar, CA Gyuricza, PA Chong, JL Wrana, J Massague, Y Shi
Science, 2000science.org
The Smad proteins mediate transforming growth factor–β (TGFβ) signaling from the
transmembrane serine-threonine receptor kinases to the nucleus. The Smad anchor for
receptor activation (SARA) recruits Smad2 to the TGFβ 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 α helix, and a β strand, interacts with the β sheet and …
The Smad proteins mediate transforming growth factor–β (TGFβ) signaling from the transmembrane serine-threonine receptor kinases to the nucleus. The Smad anchor for receptor activation (SARA) recruits Smad2 to the TGFβ 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 α helix, and a β strand, interacts with the β sheet and the three-helix bundle of Smad2. Recognition between the SARA rigid coil and the Smad2 β sheet is essential for specificity, whereas interactions between the SARA β 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.
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