Three-finger toxin fold for the extracellular ligand-binding domain of the type II activin receptor serine kinase.
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.
Greenwald
J
J
Structural Biology Laboratory, The Salk Institute, La Jolla, California 92037, USA.
Fischer
W H
WH
Vale
W W
WW
Choe
S
S
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
D008024:Ligands; D017978:Receptors, Growth Factor; D028341:Activins; D007265:Inhibins; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors