Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Procognia (Israel) Ltd., Ashdod, Israel.
Mol Cell Endocrinol. 2014 Feb 15;382(2):781-90. doi: 10.1016/j.mce.2013.10.032. Epub 2013 Nov 12.
CGβ subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. It has evolved by incorporating a previously untranslated region of the LHβ gene into the reading frame. Although CTP-like sequences are encrypted in the LHβ genes of several mammals, the CGβ subunit developed only in primates and equids. To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. The boCTP does not impede several crucial aspects of hormone biosynthesis, but compared to the hCGβ-CTP, the stretch lacks O-glycans and determinants for circulatory survival. O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. This may explain why LH did not evolve into CG in ruminants and consequently alternative mechanisms evolved to delay luteolysis early in gestation.
CGβ亚基包含一个独特的羧基末端肽（CTP），具有多个 O-连接聚糖，并延长了蛋白质的血清半衰期。它通过将 LHβ 基因的先前未翻译区域纳入阅读框而进化而来。尽管在几种哺乳动物的 LHβ 基因中都加密了类似 CTP 的序列，但 CGβ 亚基仅在灵长类动物和马科动物中发展。为了研究这种进化限制，我们研究了从牛 LHβ 基因（boCTP）解码的隐藏 CTP 是否具有人（h）CGβ-CTP 的关键特征。boCTP 不会阻碍激素生物合成的几个关键方面，但与 hCGβ-CTP 相比，该延伸缺乏 O-聚糖和循环存活的决定因素。O-聚糖缺乏以及相关的不能延长血清半衰期是 boCTP 的主要缺点。这可能解释了为什么 LH 在反刍动物中没有进化成 CG，因此进化出了替代机制来延迟妊娠早期的黄体溶解。
