Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins
Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins
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DOI：
10.1016/s0896-6273(01)00512-8
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发表时间：
2001-11-20
期刊：
影响因子：
16.2
通讯作者：
De Strooper, B
中科院分区：
文献类型：
--
作者：
Annaert, WG;Esselens, C;De Strooper, B
早老素1和2的羧基末端(PS1和PS2)与大脑中神经元特异性细胞黏附分子端脑(TLN)结合。PS1缺乏导致TLN在一个尚未确定的细胞内的异常积聚。PS1的第一个跨膜区和羧基末端与TLN的跨膜区形成结合口袋。值得注意的是，APP通过其跨膜域的一部分与相同的区域结合，该跨膜域包含在家族性阿尔茨海默病中突变的关键残基。我们的数据令人惊讶地表明，PSS中关键天冬氨酸附近的结合部位和建议的催化部位之间存在空间解离。它们为支持PS的环状结构模型提供了重要的实验证据。
The carboxyl terminus of presenilin 1 and 2 (PS1 and PS2) binds to the neuron-specific cell adhesion molecule telencephalin (TLN) in the brain. PS1 deficiency results in the abnormal accumulation of TLN in a yet unidentified intracellular compartment. The first transmembrane domain and carboxyl terminus of PS1 form a binding pocket with the transmembrane domain of TLN. Remarkably, APP binds to the same regions via part of its transmembrane domain encompassing the critical residues mutated in familial Alzheimer's disease. Our data surprisingly indicate a spatial dissociation between the binding site and the proposed catalytic site near the critical aspartates in PSs. They provide important experimental evidence to support a ring structure model for PS.