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The lipidome associated with the γ-secretase complex is required for its integrity and activity

Ayciriex, Sophie and Gerber, Hermeto and Osuna, Guillermo M. Garcia and Chami, Mohamed and Stahlberg, Henning and Shevchenko, Andrej and Fraering, Patrick C.. (2016) The lipidome associated with the γ-secretase complex is required for its integrity and activity. The biochemical journal, 473 (3). pp. 321-334.

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Official URL: http://edoc.unibas.ch/42161/

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Abstract

γ-Secretase is a multi-subunit membrane protease complex that catalyses the final intramembrane cleavage of the β-amyloid precursor protein (APP) during the neuronal production of amyloid-β peptides (Aβ), which are implicated as the causative agents of Alzheimer's disease (AD). In the present study, we report the reconstitution of a highly purified, active γ-secretase complex into proteoliposomes without exogenous lipids and provide the first direct evidence for the existence of a microenvironment of 53 molecular species from 11 major lipid classes specifically associated with the γ-secretase complex, including phosphatidylcholine and cholesterol. Importantly, we demonstrate that the pharmacological modulation of certain phospholipids abolishes both the integrity and the enzymatic activity of the intramembrane protease. Together, our findings highlight the importance of a specific lipid microenvironment for the structure and function of γ-secretase.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Stahlberg)
UniBasel Contributors:Stahlberg, Henning
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Portland Press
ISSN:0264-6021
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:29 Sep 2016 07:48
Deposited On:29 Sep 2016 07:48

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