Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio.

ABSTRACT:

Background

Presenilin 1(PS1) is the catalytic subunit of gamma-secretase, the enzyme responsible for the Abeta C-terminal cleavage site, which results in the production of Abeta peptides of various lengths. Production of longer forms of the Abeta peptide occur in patients with autosomal dominant Alzheimer disease (AD) due to mutations in presenilin. Many modulators of gamma-secretase function have been described. We hypothesize that these modulators act by a common mechanism by allosterically modifying the structure of presenilin.

Methodology/principal findings

To test this hypothesis we generated a genetically encoded GFP-PS1-RFP (G-PS1-R) FRET probe that allows monitoring of the conformation of the PS1 molecule in its native environment in live cells. We show that G-PS1-R

SUBMITTER: Uemura K 

PROVIDER: S-EPMC2773935 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature