The structure of tyrosine-10 favors ionic conductance of Alzheimer's disease-associated full-length amyloid-β channels.

ABSTRACT: Amyloid β (Aβ) ion channels destabilize cellular ionic homeostasis, which contributes to neurotoxicity in Alzheimer's disease. The relative roles of various Aβ isoforms are poorly understood. We use bilayer electrophysiology, AFM imaging, circular dichroism, FTIR and fluorescence spectroscopy to characterize channel activities of four most prevalent Aβ peptides, Aβ_1-42, Aβ_1-40, and their pyroglutamylated forms (AβpE_3-42, AβpE_3-40) and correlate them with the peptides' structural features. Solvent-induced fluorescence splitting of tyrosine-10 is discovered and used to assess the sequestration from the solvent and membrane insertion. Aβ_1-42 effectively embeds in lipid membranes, contains large fraction of β-sheet in a β-barrel-like struc

SUBMITTER: Karkisaval AG 

PROVIDER: S-EPMC10864385 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature