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 involves its binding to the extracellular domain of the activin type II receptor. This receptor domain contains 10 cysteine residues which are engaged in intramolecular disulfide bonds. To elucidate the structural framework of this domain we have characterized its disulfide-bonding pattern using an extracellular fragment of the receptor which binds activin A with high affinity. By combining proteolysis with mass spectroscopy and chemical sequence analysis, the disulfide connectivity was determined to be as follows: C1-C3, C2-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.
Fischer
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The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA. Fischer@salk.edu
Greenwald
J
J
Park
M
M
Craig
A G
AG
Choe
S
S
Vale
W
W
D029404:Activin Receptors; D028341:Activins; D000595:Amino Acid Sequence; D000818:Animals; D002918:Chymotrypsin / Q000378:metabolism; D003488:Cyanogen Bromide; D004220:Disulfides / Q000032:analysis*; D010450:Endopeptidases / Q000378:metabolism; D007265:Inhibins / Q000378:metabolism; D008666:Metalloendopeptidases; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D010843:Pichia / Q000235:genetics; D017978:Receptors, Growth Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014357:Trypsin / Q000378:metabolism
D004220:Disulfides; D010446:Peptide Fragments; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D028341:Activins; D007265:Inhibins; D029404:Activin Receptors; D010450:Endopeptidases; D002918:Chymotrypsin; D014357:Trypsin; D008666:Metalloendopeptidases; C058921:endoproteinase Asp-N; D003488:Cyanogen Bromide