The disulfide bond arrangement in the extracellular domain of the activin type II receptor

The initial step in the signaling cascade of the growth factor activin invo lves its binding to the extracellular domain of the activin type II recepto r. This receptor domain contains 10 cysteine residues which are engaged in intramolecular disulfide bonds. To elucidate the structural framework of th is domain we have characterized its disulfide-bonding pattern using an extr acellular fragment of the receptor which binds activin A with high affinity . By combining proteolysis with mass spectroscopy and chemical sequence ana lysis, the disulfide connectivity was determined to be as follows: C1-C3, C 2-C4, C5-C8, C6-C7, and C9-C10. A similar disulfide arrangement occurs in a family of snake toxins for which the three-dimensional structure is known.