Alzheimer's disease amyloid beta peptide 25-35 is localized in the membrane hydrocarbon core: x-ray diffraction analysis.
Alzheimer's disease (AD) neuropathology is characterized by neuritic plaques composed primarily of amyloid beta peptide (A beta). An elevation in A beta in the cerebral cortex has been implicated in the pathophysiology of AD but its mechanism of action is unknown. The addition of A beta protein to neuronal cell cultures produces changes in the activity of various membrane proteins, including ion channels and receptors, potentially as a result of intercalating into the membrane bilayer. In this study, the interactions of the A beta fragment 25-35 [A beta(25-35)] with liposomes were directly examined by small angle x-ray diffraction approaches. One-dimensional electron density profiles generated from the diffraction data demonstrated that the addition of A beta(25-35) produced a discrete increase in electron density 0-12 A from the center of the lipid bilayer. Under these conditions, the membrane concentration of A beta(25-35) was 860-fold higher than in the aqueous buffer. These findings indicate that this peptide is highly lipophilic and inserts into the membrane hydrocarbon core. Following the intercalation of A beta(25-35) to this location in the membrane, the protein fragment may interact with regulatory membrane proteins.
Mason
R P
RP
Neurosciences Research Center, Allegheny Campus, Medical College of Pennsylvania, Pittsburgh, USA.
Estermyer
J D
JD
Kelly
J F
JF
Mason
P E
PE
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D012995:Solubility; D014961:X-Ray Diffraction
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D008565:Membrane Proteins; D010446:Peptide Fragments; D010713:Phosphatidylcholines; C074636:amyloid beta-protein (25-35)