Tian Geng, Xiang Song, Noiva Robert, Lennarz William J, Schindelin Hermann
Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, NY 11794, USA.
Cell. 2006 Jan 13;124(1):61-73. doi: 10.1016/j.cell.2005.10.044.
Protein disulfide isomerase plays a key role in catalyzing the folding of secretory proteins. It features two catalytically inactive thioredoxin domains inserted between two catalytically active thioredoxin domains and an acidic C-terminal tail. The crystal structure of yeast PDI reveals that the four thioredoxin domains are arranged in the shape of a twisted "U" with the active sites facing each other across the long sides of the "U." The inside surface of the "U" is enriched in hydrophobic residues, thereby facilitating interactions with misfolded proteins. The domain arrangement, active site location, and surface features strikingly resemble the Escherichia coli DsbC and DsbG protein disulfide isomerases. Biochemical studies demonstrate that all domains of PDI, including the C-terminal tail, are required for full catalytic activity. The structure defines a framework for rationalizing the differences between the two active sites and their respective roles in catalyzing the formation and rearrangement of disulfide bonds.
蛋白质二硫键异构酶在催化分泌蛋白折叠过程中起关键作用。它具有两个插入在两个催化活性硫氧还蛋白结构域之间的无催化活性的硫氧还蛋白结构域以及一个酸性C末端尾巴。酵母PDI的晶体结构表明，四个硫氧还蛋白结构域呈扭曲的“U”形排列，活性位点在“U”的长边相对。“U”的内表面富含疏水残基，从而促进与错误折叠蛋白的相互作用。该结构域排列、活性位点位置和表面特征与大肠杆菌DsbC和DsbG蛋白二硫键异构酶惊人地相似。生化研究表明，PDI的所有结构域，包括C末端尾巴，对于完全催化活性都是必需的。该结构定义了一个框架，用于解释两个活性位点之间的差异及其在催化二硫键形成和重排中的各自作用。
