Membrane charge dependent states of the beta-amyloid fragment Abeta (16-35) with differently charged micelle aggregates.
Abeta (16-35) is the hydrophobic central core of beta-amyloid peptide, the main component of plaques found in the brain tissue of Alzheimer's disease patients. Depending on the conditions present, beta-amyloid peptides undergo a conformational transition from random coil or alpha-helical monomers, to highly toxic beta-sheet oligomers and aggregate fibrils. The behavior of beta-amyloid peptide at plasma membrane level has been extensively investigated, and membrane charge has been proved to be a key factor modulating its conformational properties. In the present work we probed the conformational behavior of Abeta (16-35) in response to negative charge modifications of the micelle surface. CD and NMR conformational analyses were performed in negatively charged pure SDS micelles and in zwitterionic DPC micelles "doped" with small amounts of SDS. To analyze the tendency of Abeta (16-35) to interact with these micellar systems, we performed EPR experiments on three spin-labeled analogues of Abeta (16-35), bearing the methyl 3-(2,2,5,5-tetramethyl-1-oxypyrrolinyl) methanethiolsulfonate spin label at the N-terminus, in the middle of the sequence and at the C-terminus, respectively. Our conformational data show that, by varying the negative charge of the membrane, Abeta (16-35) undergoes a conformational transition from a soluble helical-kink-helical structure, to a U-turn shaped conformation that resembles protofibril models.
Grimaldi
Manuela
M
Department of Pharmaceutical Sciences, University of Salerno, I-84084 Fisciano, Italy.
Scrima
Mario
M
Esposito
Cinzia
C
Vitiello
Giuseppe
G
Ramunno
Anna
A
Limongelli
Vittorio
V
D'Errico
Gerardino
G
Novellino
Ettore
E
D'Ursi
Anna Maria
AM
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry*; D002942:Circular Dichroism; D003198:Computer Simulation; D004578:Electron Spin Resonance Spectroscopy; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D013113:Spin Labels; D055672:Static Electricity
D016229:Amyloid beta-Peptides; D007202:Indicators and Reagents; D008823:Micelles; D010446:Peptide Fragments; D013113:Spin Labels; C517203:amyloid beta-protein (16-35)