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

The Smad proteins mediate transforming growth factor-beta (TGF beta) signal ing from the transmembrane serine-threonine receptor kinases to the nucleus . The Smad anchor for receptor activation (SARA) recruits Smad2 to the TGF beta receptors for phosphorylation. The crystal structure of a Smad2 MH2 do main in complex with the Smad-binding domain (SBD) of SARA has been determi ned at 2.2 angstrom resolution. SARA SBD, in an extended conformation compr ising a rigid coil, an alpha helix, and a beta strand, interacts with the b eta sheet and the three-helix bundle of Smad2 Recognition between the SARA rigid coil and the Smad2 beta sheet is essential for specificity, whereas i nteractions between the SARA beta strand and the Smad2 three-helix bundle c ontribute significantly to binding affinity. Comparison of the structures b etween Smad2 and a comediator Smad suggests a model for how receptor-regula ted Smads are recognized by the type I receptors.