Alzheimer beta-amyloid peptide 25-35: electrostatic interactions with phospholipid membranes.
The role of lipids in the aggregation of three Alzheimer model peptides was investigated with circular dichroism spectroscopy and high-sensitivity titration calorimetry under conditions of low ionic strength. In solution, the peptides beta AP(25-35)OH and beta AP(25-35Nle)NH2 exhibit a reversible random-coil<-->beta-sheet (or beta-structured aggregate) transition. Addition of lipid vesicles containing negatively charged lipids shifts the random-coil<-->beta-sheet equilibrium almost completely toward beta-sheet structure, which can be explained by the specific conditions created at the membrane surface: the cationic peptides are attracted to the negatively charged membrane, and the increase in peptide concentration together with the partial alignment of the peptide molecules then facilitates beta-sheet formation. The third peptide, beta AP-(25-35)NH2, also binds to the lipid membrane but was found to adopt an essentially random-coil structure, both with and without lipids. A quantitative characterization of the binding equilibrium was possible with high-sensitivity titration calorimetry. All three peptides exhibited exothermic binding enthalpies which varied between delta H approximately -2 kcal/mol for beta AP(25-35)OH and -8 kcal/mol for beta AP(25-35)NH2. The apparent binding constants, calculated with bulk concentrations, were large and varied between 500 and 5 x 10(4) M-1, depending on the experimental conditions. However, after correction for electrostatic charge effects using the Gouy-Chapman theory, the intrinsic binding constants were found to be constant and much smaller with K approximately 2-10 M-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Terzi
E
E
Department of Biophysical Chemistry, Biocenter of the University of Basel, Switzerland.
Hölzemann
G
G
Seelig
J
J
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002151:Calorimetry; D002942:Circular Dichroism; D004563:Electrochemistry; D008051:Lipid Bilayers; D008563:Membrane Lipids / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013816:Thermodynamics; D017186:Titrimetry
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010446:Peptide Fragments; D010743:Phospholipids; C074636:amyloid beta-protein (25-35)