Influence of membrane lipid composition on the structure and activity of γ-secretase.

ABSTRACT: γ-Secretase (GS) is a multi-subunit membrane-embedded aspartyl protease that cleaves more than 80 integral membrane proteins, including the amyloid precursor protein (APP) to produce the amyloid-β (Aβ) peptide. Oligomerization and aggregation of the 42-amino acid length Aβ isoform in the brain has been associated with the development and progression of Alzheimer's disease (AD). Based on recent experimental structural studies and using multiscale computational modeling approaches, the conformational states and protein-membrane interactions of the GS complex embedded in six homogeneous and six heterogeneous lipid bilayers were characterized. In order to identify potential lipid and cholesterol binding sites, GS regions with high lipid/cholesterol occupancy values were analyzed using atomisti

SUBMITTER: Aguayo-Ortiz R 

PROVIDER: S-EPMC11260083 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature