Structural and dynamical studies of ß-strand-membrane proteins by liquid-/solid-state NMR spectroscopy (A04)

在成功地确定了通道蛋白hVDAC1的开放状态的结构后，我们现在的目标是通过使用一个五元组VDAC1突变体来确定关闭状态的高分辨结构，该突变体的电生理行为类似于hVDAC1的关闭状态。此外，我们还将研究低聚物调节剂Anle138b在膜中和在膜中的结构。Aü和IAPP寡聚体都能诱导离子导电性，并与神经元(阿尔茨海默病)以及通过Anle138b在小鼠模型中挽救的ç细胞功能障碍和死亡(II型糖尿病)有关。

After the successful structure determination of the open state of the channel protein hVDAC1, we now aim at determining the high resolution structure of the closed state by using a quintuple VDAC1 mutant that electrophysiologically behaves like a closed state of hVDAC1. Furthermore, we will study the structure of Aß and IAPP oligomers in membranes with and without the oligomer modulator anle138b. Both Aß and IAPP oligomers induce ion conductivity and are related to neuronal (Alzheimer) as well as ß-cell dysfunction and death (type II diabetes), which is rescued in mouse models by anle138b.