Allosteric Modulation of Intact γ-Secretase Structural Dynamics.

ABSTRACT: As a protease complex involved in the cleavage of amyloid precursor proteins that lead to the formation of amyloid β fibrils implicated in Alzheimer's disease, γ-secretase is an important target for developing therapeutics against Alzheimer's disease. γ-secretase is composed of four subunits: nicastrin (NCT) in the extracellular (EC) domain, presenilin-1 (PS1), anterior pharynx defective 1, and presenilin enhancer 2 in the transmembrane (TM) domain. NCT and PS1 play important roles in binding amyloid β precursor proteins and modulating PS1 catalytic activity. Yet, the molecular mechanisms of coupling between substrate/modulator binding and catalytic activity remain to be elucidated. Recent determination of intact human γ-secretase cryo-electron microscopy structure has opened the way for a

SUBMITTER: Lee JY 

PROVIDER: S-EPMC5770568 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature