Structural characterization of follistatin: a novel follicle-stimulating hormone release-inhibiting polypeptide from the gonad.
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 cross-linked 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.
Esch
F S
FS
Laboratories for Neuroendocrinology, Salk Institute for Biological Studies, La Jolla, California 92037.
Shimasaki
S
S
Mercado
M
M
Cooksey
K
K
Ling
N
N
Ying
S
S
Ueno
N
N
Guillemin
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005260:Female; D038681:Follistatin; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D008969:Molecular Sequence Data; D010053:Ovary / Q000737:chemistry*; D013552:Swine
D038681:Follistatin; D006023:Glycoproteins; D004247:DNA