Evidence that the COOH terminus of human presenilin 1 is located in extracytoplasmic space.
Evidence that the COOH terminus of human presenilin 1 is located in extracytoplasmic space.
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有证据表明人早老素 1 的 COOH 末端位于胞质外空间。
DOI：
10.1152/ajpcell.00636.2004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Turner,RJames
中科院分区：
文献类型：
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作者：
Oh,YoungS;Turner,RJames
多位膜蛋白早老素1（PS1）是γ-分泌酶复合物的组分，其负责包括β-淀粉样前体蛋白（APP）在内的几种I型跨膜蛋白的膜内切割。PS1的突变，显然导致APP的异常加工，已与早发性家族性阿尔茨海默病遗传相关。PS1含有10个疏水区（HR），其长度足以成为α-螺旋跨膜片段。PS1的大多数拓扑结构模型将其COOH末端的1040个氨基酸（包括HR 10）置于胞质空间。然而，最近的一些观察表明，HR 10可能被整合到膜和参与PS 1和APP之间的相互作用。我们已经采用了三个独立的方法来调查的位置HR 10和极端的COOH端的PS 1。从这些方法的结果表明，HR 10跨越膜和PS 1的COOH末端氨基酸位于胞质外空间。
The polytopic membrane protein presenilin 1 (PS1) is a component of the γ-secretase complex that is responsible for the intramembranous cleavage of several type I transmembrane proteins, including the β-amyloid precursor protein (APP). Mutations of PS1, apparently leading to aberrant processing of APP, have been genetically linked to early-onset familial Alzheimer’s disease. PS1 contains 10 hydrophobic regions (HRs) sufficiently long to be α-helical membrane spanning segments. Most topology models for PS1 place its COOH terminal ∼40 amino acids, which include HR 10, in the cytosolic space. However, several recent observations suggest that HR 10 may be integrated into the membrane and involved in the interaction between PS1 and APP. We have applied three independent methodologies to investigate the location of HR 10 and the extreme COOH terminus of PS1. The results from these methods indicate that HR 10 spans the membrane and that the COOH terminal amino acids of PS1 lie in the extracytoplasmic space.