Wnt信号通路中无序蛋白DEP结构域识别的结构基础。
Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway.
作者信息
Wong H C, Mao J, Nguyen J T, Srinivas S, Zhang W, Liu B, Li L, Wu D, Zheng J
机构信息
Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
出版信息
Nat Struct Biol. 2000 Dec;7(12):1178-84. doi: 10.1038/82047.
Abstract
The DEP domain of Dishevelled (Dvl) proteins transduces signals to effector proteins downstream of Dvl in the Wnt pathway. Here we report that DEP-containing mutants inhibit Wnt-induced, but not Dvl-induced, activation of the transcription factor Lef-1. This inhibitory effect is weakened by a K434M mutation. Nuclear magnetic resonance spectroscopy revealed that the DEP domain of mouse Dvl1 comprises a three-helix bundle, a beta-hairpin 'arm' and two short beta-strands at the C-terminal region. Lys 434 is located at the tip of the beta-hairpin 'arm'. Based on our findings, we conclude that DEP interacts with regulators upstream of Dvl via a strong electric dipole on the molecule's surface created by Lys 434, Asp 445 and Asp 448; the electric dipole and the putative membrane binding site are at two different locations.
摘要
Dishevelled（Dvl）蛋白的DEP结构域将信号传导至Wnt信号通路中Dvl下游的效应蛋白。在此我们报告，含DEP结构域的突变体抑制Wnt诱导而非Dvl诱导的转录因子Lef-1的激活。这种抑制作用因K434M突变而减弱。核磁共振光谱显示，小鼠Dvl1的DEP结构域由一个三螺旋束、一个β发夹“臂”和C末端区域的两条短β链组成。赖氨酸434位于β发夹“臂”的末端。基于我们的发现，我们得出结论，DEP通过由赖氨酸434、天冬氨酸445和天冬氨酸448在分子表面形成的强电偶极与Dvl上游的调节因子相互作用；电偶极和假定的膜结合位点位于两个不同位置。
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