膜蛋白208中WH2结构域和脯氨酰羟基化基序的功能研究

膜蛋白208（TMEM208）是主要定位于内质网的跨膜蛋白，具有调节内质网应激反应和细胞自噬的作用。但是对TMEM208发挥作用的分子细节缺乏了解。我们的初步研究发现，TMEM208除了三个跨膜区外，还有两个主要特征性结构：氨基酸序列87-105位19个氨基酸是一个WH2结构域，128-141位14个氨基酸可能是一个氧依赖的脯氨酰羟基化基序。初步研究发现，TMEM208可以与肌动蛋白相互作用，过表达TMEM208可以增加细胞内的活性氧水平。本课题将在此基础上进一步研究WH2结构域在TMEM208与肌动蛋白相互作用中的功能，及脯氨酰羟基化基序在TMEM208调节细胞内活性氧中的作用，并分析TMEM208蛋白在细胞内的降解方式。本项目的实施有助于明确TMEM208蛋白中WH2结构域和脯氨酰羟基化基序的功能，通过TMEM208揭示内质网应激反应、细胞骨架、活性氧和细胞自噬之间的内在联系。

TMEM208 is an ER-located protein which can regulate both autophagy and ER stress. How TMEM208 regulates ER stress and autophagy hasn’t been determined. Besides the three transmembrane domains, we recently found TMEM208 has a WH2 domain (Wiskott–Aldrich syndrome protein Homology domain 2), correspondent to 19 amino acids from 87 to 105 amino residues, and an oxygen dependent prolyl hydroxylation motif, correspondent to 14 amino acids from 128 to 141 amino residues. We next analyzed the two structural features and functions of TMEM208. The results showed that TMEM 208 could interact with β-actin and overexpression of TMEM208 increased the level of cellular reactive oxygen. We thus wish to understand the molecular mechanisms of how the WH2 domain and prolyl hydroxylation motif of TMEM208 regulate the function of TMEM208. Our studies will offer novel insights on the interaction between ER stress, cytoskeleton, cellular reactive oxygen and autophagy.