Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor
Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor
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DOI：
10.22358/jafs/66031/2012
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发表时间：
2012-01-01
影响因子：
1
通讯作者：
Kochman, K.
中科院分区：
文献类型：
--
作者：
Kochman, K.
现在很明显，促性腺激素释放激素（GnRH）结构在动物进化的早期就已经存在，并以多种方式调节生殖。在6亿年的动物进化过程中，GnRH的N和C末端作为结合和激活同源受体以实现其功能的功能结构域一直是保守的。大约4亿年前，无颚鱼的GnRH 6位的手性氨基酸被非手性甘氨酸单次取代，促进了GnRH的II型β转角构象，使GnRH功能结构域与受体在空间上紧密相互作用，这与早期进化物种中更广泛的GnRH结构与其同源受体的相互作用相反。GnRH II通过分子内相互作用预先配置为这种构象，这解释了它的高结合亲和力和在4亿年的进化中一级结构的总体保守性。非常令人惊讶和迷人的是，参与结合GnRH的氨基酸的协调进化选择导致了如此完美的结果，即在任何位置都没有天然氨基酸的取代可以提高结合效力。
It is evident now that the gonadotropin-releasing hormone (GnRH) structure was already in existence very early in the evolution of animals and was co-opted in diverse ways to regulate reproduction. During 600 million years of animal evolution, the N and C termini of GnRH have been conserved as functional domains for binding and activating cognate receptors to accomplish its functions. About 400 millions years ago, a single substitution of the chiral amino acid in position 6 of GnRH in jawless fish by the achiral glycine facilitated a type II' beta-turn conformation of GnRH to allow spatially close interaction of functional domains of GnRH with receptors, in contrast to the interaction of more extended GnRH structures with their cognate receptors in earlier-evolved species. GnRH II was preconfigured to this conformation through intramolecular interactions, which accounts for its high binding affinity and total conservation of primary structure over 400 million years of evolution. It is very surprising and fascinating that the coordinated evolutionary selection of amino acids participating in binding GnRH has resulted in such perfection, that no substitution with a natural amino acid in any position improves binding potency.