STRUCTURAL CHARACTERIZATION OF FOLLISTATIN - A NOVEL FOLLICLE-STIMULATING-HORMONE RELEASE-INHIBITING POLYPEPTIDE FROM THE GONAD
STRUCTURAL CHARACTERIZATION OF FOLLISTATIN - A NOVEL FOLLICLE-STIMULATING-HORMONE RELEASE-INHIBITING POLYPEPTIDE FROM THE GONAD
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DOI：
10.1210/mend-1-11-849
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发表时间：
1987-11-01
影响因子：
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通讯作者：
GUILLEMIN, R
中科院分区：
文献类型：
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作者：
ESCH, FS;SHIMASAKI, S;GUILLEMIN, R
卵泡抑素是一种新的单链糖基化多肽，与已知的抑制素没有同源性，但具有强大的特异性抑制垂体FSH释放的作用，已通过蛋白质微测序、cDNA克隆和DNA测序进行了结构表征。发现两组克隆的3‘-’非翻译序列不同，分别编码344个氨基酸前体蛋白和一个相同但羧基末端截短的317个氨基酸前体。另外，一个克隆FS18含有两个内含子，可能是在构建文库的过程中异质核RNA反转录的结果。卵泡抑素富含半胱氨酸，在315个氨基酸的成熟编码序列中含有36个半胱氨酸，以及一个极端酸性的羧基末端区域FS(292-304)，它由Glu-Asp-Thr-Glu-Glu-Glu-Glu-Glu-Asp-Glu-Asp-Gln-Asp组成，可能存在于紧密交联的蛋白质球体之外。卵泡抑素的肝素结合能力可能归因于FS(75-86)，Lys-Lys-Cys-Arg-Met-Asn-Lys-Lys-Asn-Lys的碱性区域。总体而言，卵泡抑素被组织成三个同源结构域，FS(66-135)、FS(139-210)和FS(216-287)，分别包含70、72和72个氨基酸，它们之间有52%的同源性，当与56个氨基酸的人胰腺分泌胰蛋白酶抑制蛋白进行最大同源性比对时，有57%的同源性。
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.