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Publication Abstract from PubMed

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.

The structure of the follistatin:activin complex reveals antagonism of both type I and type II receptor binding.,Thompson TB, Lerch TF, Cook RW, Woodruff TK, Jardetzky TS Dev Cell. 2005 Oct;9(4):535-43. PMID:16198295^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.