Influence of the lipid environment on the accessibility of the APP684-726 alpha-cleavage site

As found for P-gp, the function and activity of particular membrane proteins is controlled by the characteristics of the lipid environment. The lipid bilayer composition varies between organs, cells, organelles and membrane micro domains and is furthermore dependent on age, sex, nutrition and life style. Choosing the amyloid precursor protein (APP) as a model, we study the influence of the lipid bilayer composition on the processing of membrane proteins. The amyloid beta (A-beta) is a major hallmark of Alzheimer’s Disease being involved in the formation of extracellular plaques. A-beta is generated from APP after cleavage by the beta- and gamma-secretases, while cleavage by the alpha-secretase prevents its production. According to the putative transmembrane domain of APP, the alpha-cleavage site is in close vicinity to the membrane surface. The mobility and accessibility of the corresponding amino acid sequence of synthesized APP684-726 incorporated in liposomes of different lipid composition is studied with biochemical methods and by solid state NMR in collaboration with the Laboratory of Physical Chemistry at ETH.

ETH Research Database: id 13633

Contacts: Prof. Dr. Beat Meier,  Prof. Dr. Heidi Wunderli-Allenspach, Dr. Stefanie Krämer