抗穆勒尔激素亲复合体非潜伏信号的结构基础
James A Howard1, Lucija Hok2, Richard L Cate3
1Department of Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, United States.
bioRxiv : the preprint server for biology
|April 15, 2024
概括
抗穆勒尔激素 (AMH) 产区将其生长因子 (GF) 紧密结合,但仍然活跃. 结构分析揭示了一个独特的GF结合域,在受体结合时经历了构造变化,从而使信号传递成为可能.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子内分泌学分子内分泌学
背景情况:
- 转化生长因子-β (TGFβ) 家庭连接体通常与调节其活动的原域形成复合体.
- 抗穆勒尔激素 (AMH) 是独一无二的,其原域保持了对生长因子 (GF) 的高度亲和力,同时允许活性.
研究的目的:
- 阐明AMH原域与其生长因子 (GF) 独特相互作用的结构基础.
- 了解AMH前域在高亲缘关系结合的情况下促进信号传输的机制.
主要方法:
- 使用单粒子电子显微镜 (EM) 来确定AMH复合体的结构.
- 分析的重点是AMH GF与其原域结合时的构造,以及受体参与的影响.
主要成果:
- 该AMH原域包括一个TGFβ类折叠和一个新的螺旋捆GF结合域.
- 这种GF结合域参与AMH受体 (AMHR2) 表位.
- 当AMH GF与产域结合时,它采用了紧张的开放形状,当产域结合时,产域在受体结合时被关闭,从而取代产域.
结论:
- 对AMH受体2 (AMHR2) 的双相结合触发了构造性转移,将原域位移.
- 这种位移机制对于启动AMH信号发送至关重要,它与其他TGFβ连接体不同.
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