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Laboratories for Neuroendocrinology, Salk Institute for Biological Studies La Jolla, California 92037
Address requests for reprints to: F. S. Esch, Laboratories for Neuroendocrinology, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037.
Abstract
Follistatin, a novel, single chain, glycosylated polypeptide bearing no homology with previously characterized inhibins but exhibiting potent and specific pituitary FSH-release inhibition has been structurally characterized by protein microsequencing, cDNA cloning, and DNA sequencing. Two populations of clones differing in their 3'-untranslated sequences were found to encode a 344 amino acid precursor protein and an identical but carboxyl terminal truncated 317 amino acid precursor, respectively. Additionally, one clone, FS18, contained two introns and probably resulted from reverse transcription of heterogeneous nuclear RNA during cDNA library construction. Follistatin is unusually cysteine-rich, containing 36 cysteines in the mature coding sequence of 315 amino acids and an extremely acidic carboxyl terminal region, FS(292-304), comprised of Glu-Asp-Thr-Glu-Glu-Glu-Glu-Glu-Asp-Glu-Asp-Gln-Asp which probably resides outside a tightly crosslinked protein sphere. The heparin-binding ability of follistatin can probably be ascribed to the basic region specified by FS(75-86), Lys-Lys-Cys-Arg-Met-Asn-Lys-Lys-Asn-Lys. Overall, follistatin is organized into three homologous domains, FS(66-135), FS(139-210), and FS(216-287) containing 70, 72, and 72 amino acids, respectively, which show a 52% homology among themselves and a 57% homology with the 56 amino acid human pancreatic secretory trypsin inhibitor protein when aligned for maximum homology.
FOOTNOTES
This research was supported by NICHD Contract N01HD-6-2944, Program Project Grants HD-09690 and DK-18811 from the NIH, and a grant from the Robert J. and Helen C. Kleberg Foundation.
* Present address: Athena Neurosciences Inc., 887-D Industrial Road, San Carlos, CA 94070.
Received for publication August 21, 1987. Accepted for publication September 7, 1987.
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