Toward Structural Elucidation of the γ-Secretase Complex

被引：57

作者：

Li, Huilin ^{[1
,2
]}

Wolfe, Michael S. ^{[3
,4
]}

Selkoe, Dennis J. ^{[3
,4
]}

机构：

[1] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA

[2] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA

[3] Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Boston, MA 02115 USA

来源：

STRUCTURE | 2009年 / 17卷 / 03期

基金：

美国国家卫生研究院;

关键词：

ALZHEIMERS-DISEASE; PRESENILIN ENDOPROTEOLYSIS; INTRAMEMBRANE PROTEOLYSIS; TRANSMEMBRANE DOMAIN; MEMBRANE TOPOLOGY; CRYSTAL-STRUCTURE; BETA-SECRETASE; PROTEIN; NICASTRIN; APH-1;

D O I：

10.1016/j.str.2009.01.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

gamma-Secretase is an intramembrane protease complex that mediates the Notch signaling pathway and the production of amyloid beta-proteins. As such, this enzyme has emerged as an important target for development of novel therapeutics for Alzheimer disease and cancer. Great progress has been made in the identification and characterization of the membrane complex and its biological functions. One major challenge now is to illuminate the structure of this fascinating and important protease at atomic resolution. Here, we review recent progress on biochemical and biophysical probing of the structure of the four-component complex and discuss obstacles and potential pathways toward elucidating its detailed structure.

引用

页码：326 / 334

页数：9

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