2B0U : The Structure of the Follistatin:Activin Complex

  • Thomas B. Thompson (Contributor)
  • Thomas F. Lerch (Contributor)
  • Robert W. Cook (Contributor)
  • Teresa K. Woodruff (Contributor)
  • Theodore S. Jardetzky (Contributor)



Experimental Technique/Method:X-RAY DIFFRACTION
Release Date:2005-10-11
Deposition Date:2005-09-14
Revision Date:2008-05-01#2011-07-13#2011-07-27#2017-10-11
Molecular Weight:90655.59
Macromolecule Type:Protein
Residue Count:808
Atom Site Count:5904

TGF-beta ligands stimulate diverse cellular differentiation and growth responses by signaling through type I and II receptors. Ligand antagonists, such as follistatin, block signaling and are essential regulators of physiological responses. Here we report the structure of activin A, a TGF-beta ligand, bound to the high-affinity antagonist follistatin. Two follistatin molecules encircle activin, neutralizing the ligand by burying one-third of its residues and its receptor binding sites. Previous studies have suggested that type I receptor binding would not be blocked by follistatin, but the crystal structure reveals that the follistatin N-terminal domain has an unexpected fold that mimics a universal type I receptor motif and occupies this receptor binding site. The formation of follistatin:BMP:type I receptor complexes can be explained by the stoichiometric and geometric arrangement of the activin:follistatin complex. The mode of ligand binding by follistatin has important implications for its ability to neutralize homo- and heterodimeric ligands of this growth factor family.
Date made available2005

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