Verification of the intermolecular parallel beta-sheet in E22K-Abeta42 aggregates by solid-state NMR using rotational resonance: implications for the supramolecular arrangement of the toxic conformer of Abeta42.
Formation of the intermolecular beta-sheet is a key event in the aggregation of 42-residue amyloid-beta (Abeta42). We have recently identified a physiological and toxic conformer, the turn positions of which are slightly different from each other, in the aggregates of E22K-Abeta42 (one of the mutants related to cerebral amyloid angiopathy). However, it remains unclear whether the intermolecular beta-sheet in the E22K-Abeta42 aggregates is parallel or antiparallel. We prepared an equal mixture of E22K-Abeta42 aggregates labeled at C(alpha) and those labeled at C=O with (13)C, whose intermolecular (13)C-(13)C distance was estimated by solid-state NMR using rotational resonance (R2). The intermolecular proximity of beta-strands at positions 21 and 30 was less than 6 A, supporting the existence of the intermolecular parallel beta-sheet in the E22K-Abeta42 aggregates as well as in wild-type Abeta42 aggregates. The results also suggest that each conformer would not accumulate alternately, but form a relatively large assembly.
Masuda
Yuichi
Y
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Japan.
Nakanishi
Azusa
A
Ohashi
Ryutaro
R
Takegoshi
Kiyonori
K
Shimizu
Takahiko
T
Shirasawa
Takuji
T
Irie
Kazuhiro
K
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D018698:Glutamic Acid / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D018698:Glutamic Acid; D008239:Lysine