Interactions of amyloid beta-peptide (1-40) with ganglioside-containing membranes.
Interactions between amyloid beta-peptides (Abeta) and neuronal membranes have been postulated to play an important role in the neuropathology of Alzheimer's disease. To gain insight into the molecular details of this association, we investigated the interactions of Abeta (1-40) with ganglioside-containing membranes by circular dichroism (CD) and Fourier transform infrared-polarized attenuated total reflection (FTIR-PATR) spectroscopy. The CD study revealed that at physiological ionic strength Abeta (1-40) specifically binds to ganglioside-containing membranes inducing a two-state, unordered --> beta-sheet transition above a threshold intramembrane ganglioside concentration, which depends on the host lipid bilayers used. Furthermore, differences in the number and position of sialic acid residues of the carbohydrate backbone significantly affected the conformational transition of the peptide. FTIR-PATR spectroscopy experiments demonstrated that Abeta (1-40) forms an antiparallel beta-sheet, the plane of which lies parallel to the membrane surface, inducing dehydration of lipid interfacial groups and perturbation of acyl chain orientation. These results suggest that Abeta (1-40) imposes negative curvature strain on ganglioside-containing lipid bilayers, disturbing the structure and function of the membranes.
Matsuzaki
K
K
Graduate School of Pharmaceutical Science, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. katsumim@pharm.kyoto-u.ac.jp
Horikiri
C
C
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; C078592:amyloid beta-protein (1-40); D005677:G(M1) Ganglioside