Positioning of the Alzheimer Abeta(1-40) peptide in SDS micelles using NMR and paramagnetic probes.
NMR spectroscopy combined with paramagnetic relaxation agents was used to study the positioning of the 40-residue Alzheimer Amyloid beta-peptide Abeta(1-40) in SDS micelles. 5-Doxyl stearic acid incorporated into the micelle or Mn(2+) ions in the aqueous solvent were used to determine the position of the peptide relative to the micelle geometry. In SDS solvent, the two alpha-helices induced in Abeta(1-40), comprising residues 15-24, and 29-35, respectively, are surrounded by flexible unstructured regions. NMR signals from these unstructured regions are strongly attenuated in the presence of Mn(2+) showing that these regions are positioned mostly outside the micelle. The central helix (residues 15-24) is significantly affected by 5-doxyl stearic acid however somewhat less for residues 16, 20, 22 and 23. This alpha-helix therefore resides in the SDS headgroup region with the face with residues 16, 20, 22 and 23 directed away from the hydrophobic interior of the micelle. The C-terminal helix is protected both from 5-doxyl stearic acid and Mn(2+), and should be buried in the hydrophobic interior of the micelle. The SDS micelles were characterized by diffusion and (15)N-relaxation measurements. Comparison of experimentally determined translational diffusion coefficients for SDS and Abeta(1-40) show that the size of SDS micelle is not significantly changed by interaction with Abeta(1-40).
Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm 106 91, Sweden. jyri.jarvet@dbb.su.se
Jüri
J
Jarvet
Jens
J
Danielsson
Peter
P
Damberg
Marta
M
Oleszczuk
Astrid
A
Gräslund
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002247:Carbon Isotopes; D004058:Diffusion; D008280:Magnetics / Q000295:instrumentation*; D008823:Micelles; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011522:Protons; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D002247:Carbon Isotopes; D008823:Micelles; D010446:Peptide Fragments; D010455:Peptides; D011522:Protons; C078592:amyloid beta-protein (1-40); D012967:Sodium Dodecyl Sulfate