Three-finger toxin fold for the extracellular ligand-binding domain of the type II activin receptor serine kinase

Nat Struct Biol. 1999 Jan;6(1):18-22. doi: 10.1038/4887.


The transforming growth factor beta (TGFbeta) superfamily of cytokines elicit diverse biological responses by interacting with two distinct, but structurally related transmembrane receptor serine kinases (type I and type II). The binding of these dimeric ligands to the type II receptor is the first event in transmembrane signaling for this family. Here we report the 1.5 A resolution crystal structure of the extracellular ligand-binding domain of the type II activin receptor (ActRII-ECD), which reveals a fold similar to that of a class of toxins known as three-finger toxins. This fold is primarily dictated by disulfide bonds formed by eight conserved cysteines, with a characteristic spacing, and thus is likely to be shared by most of the type I and II receptors for the TGFbeta family. Sequence comparison with an evolutionarily distant activin binding-protein identifies several conserved residues, including two hydrophobic clusters that may form binding surfaces for activin and the type I receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Activin Receptors
  • Activins
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Humans
  • Inhibins / chemistry
  • Inhibins / metabolism
  • Ligands
  • Molecular Sequence Data
  • Protein Binding
  • Protein Folding
  • Protein-Serine-Threonine Kinases / chemistry*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Growth Factor / chemistry*
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / metabolism
  • Sequence Alignment
  • Sequence Analysis


  • Ligands
  • Receptors, Growth Factor
  • Activins
  • Inhibins
  • Protein-Serine-Threonine Kinases
  • Activin Receptors

Associated data

  • PDB/1BTE