Nov 4, 2017

Recruitment of the amyloid precursor protein by γ-secretase at the synaptic plasma membrane

Biochemical and Biophysical Research Communications
Martina AudagnottoMatteo Dal Peraro

Abstract

Γ-secretase is a membrane-embedded protease that cleaves single transmembrane helical domains of various integral membrane proteins. The amyloid precursor protein (APP) is an important substrate due to its pathological relevance to Alzheimer's disease. The mechanism of the cleavage of APP by γ-secretase that leads to accumulation of Alzheimer's disease causing amyloid-β (Aβ) is still unknown. Coarse-grained molecular dynamics simulations in this study reveal initial lipids raft formation near the catalytic site of γ-secretase as well as changes in dynamic behavior of γ-secretase once interacting with APP. The results suggest a precursor of the APP binding mode and hint at conformational changes of γ-secretase in the nicastrin (NCT) domain upon APP binding.

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Mentioned in this Paper

Molecular Dynamics
Study
APP protein, human
Cleaved
Integral Membrane Proteins
Peptide Hydrolases
Amyloid Beta Precursor Protein Measurement
Cytokinesis of the Fertilized Ovum
Endopeptidases
Integral to Membrane

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