Verification of the C-terminal intramolecular beta-sheet in Abeta42 aggregates using solid-state NMR: implications for potent neurotoxicity through the formation of radicals.
Structural analysis of 42-residue amyloid beta (Abeta42) aggregates using rotational resonance in solid-state NMR verified that C(beta) and/or C(gamma) of Met-35 and the carboxyl carbon of Ala-42 are proximal enough to form an intramolecular antiparallel beta-sheet in the C-terminus. The S-oxidized radical cation at Met-35, an ultimate radical species responsible for neurotoxicity, could be stabilized by the carboxylate anion at the C-terminus, resulting in aggregation to cause long-term oxidative stress.
Masuda
Yuichi
Y
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Uemura
Satoko
S
Nakanishi
Azusa
A
Ohashi
Ryutaro
R
Takegoshi
K
K
Shimizu
Takahiko
T
Shirasawa
Takuji
T
Irie
Kazuhiro
K
D000409:Alanine / Q000737:chemistry; D000544:Alzheimer Disease / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D008715:Methionine / Q000737:chemistry; D008954:Models, Biological; D008958:Models, Molecular; D020258:Neurotoxicity Syndromes; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D018384:Oxidative Stress / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D005609:Free Radicals; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D008715:Methionine; D000409:Alanine