title: Three-finger toxin fold for the extracellular ligand-binding domain of the type II activin receptor serine kinase.
abstract: 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.
authors.affiliation: Structural Biology Laboratory, The Salk Institute, La Jolla, California 92037, USA.
authors.forename: J
authors.initials: J
authors.lastname: Greenwald
authors.forename: W H
authors.initials: WH
authors.lastname: Fischer
authors.forename: W W
authors.initials: WW
authors.lastname: Vale
authors.forename: S
authors.initials: S
authors.lastname: Choe
mesh_terms: D029404:Activin Receptors; D028341:Activins; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D007265:Inhibins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D011485:Protein Binding; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017421:Sequence Analysis
chemical_list: D008024:Ligands; D017978:Receptors, Growth Factor; D028341:Activins; D007265:Inhibins; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors