Perturbations of the straight transmembrane α-helical structure of the amyloid precursor protein affect its processing by γ-secretase.

ABSTRACT: The amyloid precursor protein (APP) is a widely expressed type I transmembrane (TM) glycoprotein present at the neuronal synapse. The proteolytic cleavage by γ-secretase of its C-terminal fragment produces amyloid-β (Aβ) peptides of different lengths, the deposition of which is an early indicator of Alzheimer disease. At present, there is no consensus on the conformation of the APP-TM domain at the biological membrane. Although structures have been determined by NMR in detergent micelles, their conformation is markedly different. Here we show by using molecular simulations that the APP-TM region systematically prefers a straight α-helical conformation once embedded in a membrane bilayer. However, APP-TM is highly flexible, and its secondary structure is strongly influenced by the surroundi

SUBMITTER: Lemmin T 

PROVIDER: S-EPMC3945338 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature