Dynamics and Cleavability at the α-Cleavage Site of APP(684-726) in Different Lipid Environments

AbstractThe occurrence of late-onset Alzheimer's disease has been related to the lipid homeostasis. We tested whether the membrane lipid environment affects the dynamics and cleavability of a model peptide corresponding to the amino acid sequence 684–726 of the amyloid precursor protein APP reconstituted in liposomes. Solid-state NMR with 2H-Ala713, which is located within the putative transmembrane domain, suggested that the peptide observes less rotational motion in egg phosphatidylcholine (PhC) membranes than in dimyristoyl-phosphatidylcholine (DMPC) bilayers above the main phase transition temperature Tc. The residue 15N-Ala692, which is in the vicinity of the α-cleavage site, i.e., Lys687, showed less motion after reconstitution in distearoyl-phosphatidylcholine liposomes