果蝇胚胎发育中的淀粉样组装参与激活磷酸酶，这一成果由美国斯托尔斯医学研究所Kausik Si研究组取得。该项研究成果发表在2019年9月5日出版的《细胞》上。

研究人员通过黑腹果蝇（Drosophila melanogaster）的多模式筛选鉴定到一个朊蛋白样蛋白Herzog（CG5830）。Herzog作为膜相关磷酸酶起作用并控制胚胎模式话，可能参与TGF-β/BMP和FGF/EGF信号传导途径。值得注意的是，Herzog单体是没有酶活的的而在淀粉样蛋白样组装后变得具有活性。Herzog的朊蛋白样结构域对于其组装和膜定位是必需的。去除朊蛋白样结构域会影响活性，同时使用异源朊蛋白样结构域能够恢复膜上的组装并且膜定位模体能够恢复磷酸酶活性。这项研究提供了朊蛋白样结构域研究的实例，其允许酶通过淀粉样组装获得基本功能以控制动物发育。

据了解，朊蛋白样蛋白可以在同一细胞中呈现不同的构象和物理状态。序列分析表明朊蛋白样蛋白在各种物种中普遍存在；然而，目前尚不清楚它们在多细胞生物中具有的功能。

附：英文原文

Title: Amyloid-like Assembly Activates a Phosphatase in the Developing Drosophila Embryo

Author: Zelha Nil, Rubén Hervás Millán, Therese Gerbich, Paulo Leal, Zulin Yu, Anita Saraf, Mihaela Sardiu, Jeffrey J. Lange, Kexi Yi, Jay Unruh, Brian Slaughter, Kausik Si

Issue&Volume:Volume 178 Issue 6

Abstract: Prion-like proteins can assume distinct conformational and physical states in the same cell. Sequence analysis suggests that prion-like proteins are prevalent in various species; however, it remains unclear what functional space they occupy in multicellular organisms. Here, we report the identification of a prion-like protein, Herzog (CG5830), through a multimodal screen in Drosophila melanogaster. Herzog functions as a membrane-associated phosphatase and controls embryonic patterning, likely being involved in TGF-β/BMP and FGF/EGF signaling pathways. Remarkably, monomeric Herzog is enzymatically inactive and becomes active upon amyloid-like assembly. The prion-like domain of Herzog is necessary for both its assembly and membrane targeting. Removal of the prion-like domain impairs activity, while restoring assembly on the membrane using a heterologous prion-like domain and membrane-targeting motif can restore phosphatase activity. This study provides an example of a prion-like domain that allows an enzyme to gain essential functionality via amyloid-like assembly to control animal development.

DOI: 10.1016/j.cell.2019.08.019

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30907-9