Structural basis for a functional antagonist in the transforming growth factor β superfamily
Structural basis for a functional antagonist in the transforming growth factor β superfamily
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DOI：
10.1074/jbc.m504591200
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发表时间：
2005-12-02
影响因子：
4.8
通讯作者：
Wookdruff, TK
中科院分区：
文献类型：
--
作者：
Cook, RW;Thompson, TB;Wookdruff, TK
在转化生长因子β超家族中，激活素和β-胡萝卜素之间的激动剂-拮抗剂关系是独特的，对综合生殖功能至关重要。激活素在垂体中起作用以刺激促卵泡激素，并被内分泌作用的、性腺衍生的促卵泡激素拮抗。我们已经进行了激活素β A亚基的突变分析，以确定有助于激活素拮抗作用的精确结构方面。通过用来自α亚基的类似对齐的氨基酸取代激活素β A亚基中的特定氨基酸残基，我们已经确定了激活素受体结合和活性以及激活素通过其受体的β受体拮抗作用所需的残基。此外，我们已经确定了一个激活素突变体与激活素I型受体的亲和力更高，提供了转化生长因子β超家族内的配体-受体相互作用的演变的结构证据。
Within the transforming growth factor beta superfamily, the agonist-antagonist relationship between activin and inhibin is unique and critical to integrated reproductive function. Activin acts in the pituitary to stimulate follicle-stimulating hormone, and is antagonized by endocrine acting, gonadally derived inhibin. We have undertaken a mutational analysis of the activin beta A subunit to determine the precise structural aspects that contribute to inhibin antagonism of activin. By substituting specific amino acid residues in the activin beta A subunit with similarly aligned amino acids from the alpha subunit, we have pinpointed the residues required for activin receptor binding and activity, as well as for inhibin antagonism of activin through its receptors. Additionally, we have identified an activin mutant with a higher affinity for the activin type I receptor that provides structural evidence for the evolution of ligand-receptor interactions within the transforming growth factor beta superfamily.