Structural and dynamic features of Alzheimer's Abeta peptide in amyloid fibrils studied by site-directed spin labeling.
Electron paramagnetic resonance spectroscopy analysis of 19 spin-labeled derivatives of the Alzheimer's amyloid beta (Abeta) peptide was used to reveal structural features of amyloid fibril formation. In the fibril, extensive regions of the peptide show an in-register, parallel arrangement. Based on the parallel arrangement and side chain mobility analysis we find the amyloid structure to be mostly ordered and specific, but we also identify more dynamic regions (N and C termini) and likely turn or bend regions (around residues 23-26). Despite their different aggregation properties and roles in disease, the two peptides, Abeta40 and Abeta42, homogeneously co-mix in amyloid fibrils suggesting that they possess the same structural architecture.
Department of Biochemistry and Molecular Biology, Neurogenetic Institute and Arnold and Mabel Beckman Macular Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Marianna
M
Török
Saskia
S
Milton
Rakez
R
Kayed
Peng
P
Wu
Theresa
T
McIntire
Charles G
CG
Glabe
Ralf
R
Langen
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008969:Molecular Sequence Data; D013113:Spin Labels
D000682:Amyloid; D016229:Amyloid beta-Peptides; D013113:Spin Labels