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

在通道蛋白hVDAC 1的开放状态的成功结构测定之后，我们现在的目标是通过使用电生理学行为类似于hVDAC 1的闭合状态的五元组VDAC 1突变体来确定闭合状态的高分辨率结构。此外，我们将研究在有和没有低聚物调节剂anle138b的膜中的AAPs和IAPP低聚物的结构。A β和IAPP寡聚体均可诱导离子导电性，并与神经元（阿尔茨海默病）以及β细胞功能障碍和死亡（II型糖尿病）有关，后者在小鼠模型中被anle 138 b所拯救。

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.