Research Article

Structural Basis of Smad2 Recognition by the Smad Anchor for Receptor Activation

Science  07 Jan 2000:
Vol. 287, Issue 5450, pp. 92-97
DOI: 10.1126/science.287.5450.92

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Abstract

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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: yshi{at}molbio.princeton.edu

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