Follistatin  (激活素结合蛋白)

Follistatin (FST) 是 TGFβ 家族信号传导的调节剂，通过选择性结合 TGFβ 家族配体并阻止配体与受体复合物结合而发挥作用。Follistatin 具有抑制促卵泡激素 (FSH) 的能力。Follistatin 首先被描述为存在于卵巢卵泡液中的促卵泡激素抑制物质。Follistatin 以低纳摩尔 (nM) 亲和力结合激活素 A 和肌肉生长抑制素，完全包围配体，封闭所有受体结合位点并与配体结合^[1][2]。
Follistatin 是一种 32-35-kDa 糖蛋白，由四个结构域组成，包括一个 N 末端结构域 (ND)，然后是三个卵泡抑素结构域 (FSD1、FSD2 和 FSD3)。Follistatin 的 C 末端剪接可产生各种同工型，包括 FS288 和 FS315。Follistatin 通过包围配体并阻止与 TGFβ 受体的相互作用形成几乎不可逆的非信号复合物，从而中和 TGFβ 配体、myostatin 和激活素 A。在人类中，编码卵泡抑素的基因位于染色体 5q11.2 上。Follistatin 含有一个 TGF-β 结合位点，在该位点激活素、骨形态蛋白 (BMP) 和生长分化因子 (GDF) 以高亲和力结合并因此被中和。Follistatin 的配体结合位点与这些配体的 I 型和 II 型受体结合位点重叠。Follistatin 还包含肝素结合位点，细胞外基质中的蛋白聚糖可以在该位点结合，因此认为卵泡抑素与细胞外基质结合。Follistatin 有两种主要的同工型，FST288 通过与硫酸肝素蛋白多糖的相互作用锚定在细胞表面，FST315 是循环中发现的主要形式。这两种亚型来自可变剪接； 315 异构体包括一个 27 个氨基酸的 C 末端酸性尾，而 Follistatin 288 没有。Follistatin 315 上的酸性尾部会中和肝素结合位点，从而抑制 Follistatin 315 与细胞外基质的结合^[1][2][3]。

Follistatin (FST) is a regulator of TGFβ family signaling and acts by selectively binding to TGFβ family ligands and preventing ligand binding to the receptor complex. Follistatin has the ability to suppress the follicle stimulating hormone (FSH). Follistatin is first described as a follicle-stimulating hormone inhibiting substance present in ovarian follicular fluid. Follistatin binds activin A and myostatin with low nanomolar (nM) affinity, completely surrounds the ligand occluding all of the receptor binding sites and binds to the ligand^[1][2]. Follistatin is a 32-35-kDa glycoprotein composed of four domains including an N-terminal domain (ND) followed by three follistatin domains (FSD1, FSD2, and FSD3). C-terminal splicing of follistatin can occur to generate various isoforms including FS288 and FS315. Follistatin neutralizes the TGFβ ligands, myostatin and activin A, by forming a nearly irreversible non-signaling complex by surrounding the ligand and preventing interaction with TGFβ receptors. In humans, the gene encoding follistatin is located on chromosome 5q11.2. The follistatin protein contains a TGF-β binding site where activins, bone morphonegic proteins (BMPs) and growth differentiation factors (GDFs) are bound with high affinity and thereby neutralised. The ligand binding site for follistatin overlaps with the type I and type II receptor binding sites for these ligands. Follistatin also contains a heparin binding site where proteoglycans in the extracellular matrix can bind, and therefore follistatin is believed to bind the extracellular matrix. There are two major isoforms of FST, FST288, which is anchored to the cell surface by interactions with heparin sulfate proteoglycans, and FST315, which is the predominant form found in circulation. The two isoforms arise from alternative splicing; the 315 isoform includes a 27 amino acid acidic C-terminal tail, which follistatin 288 does not have. The acidic tail on follistatin 315 neutralises the heparin binding site, thereby inhibiting the binding of follistatin 315 to the extracellular matrix^[1][2][3].

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