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Distance Measurement between Tyr10 and Met35 in Amyloid β by Site‐Directed Spin‐Labeling ESR Spectroscopy: Implications for the Stronger Neurotoxicity of Aβ42 than Aβ40
Author(s) -
Murakami Kazuma,
Hara Hideyuki,
Masuda Yuichi,
Ohigashi Hajime,
Irie Kazuhiro
Publication year - 2007
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200700240
Subject(s) - chemistry , neurotoxicity , spectroscopy , intramolecular force , nuclear magnetic resonance spectroscopy , nitroxide mediated radical polymerization , stereochemistry , organic chemistry , toxicity , physics , quantum mechanics , radical polymerization , copolymer , polymer
The neurotoxicity of the 42‐mer and 40‐mer amyloid β peptides (Aβ42 and Aβ40) is closely related to the radicalization at both Tyr10 and Met35. Aβ42 is more neurotoxic than Aβ40. Our previous structural analyses of Aβ42 suggested that Tyr10 and Met35 are brought closer together by the turn at positions 22 and 23, and the S‐oxidized radical cation at position 35, which is the ultimate toxic radical species, can be produced effectively through oxidation by the phenoxy radical at position 10. To verify this idea, their separation was measured by site‐directed spin labeling (MTSSL) by using ESR spectroscopy. Among the three kinds of Aβ42 derivatives, which are doubly or singly spin‐labeled at position 10 and 35, only 10,35‐MTSSL‐Aβ42 showed a clear dipole coupling in continuous‐wave ESR; this suggests that the intramolecular spin labels at position 10 and 35 in Aβ42 are located within ∼15 Å. In contrast, 10,35‐MTSSL‐Aβ40 did not give such signals. The distance between Tyr10 and Met35 in 10,35‐MTSSL‐Aβ40, which was successfully measured by pulsed ESR spectroscopy was 30 Å long. The difference in the distance between Aβ42 and Aβ40 could explain in part the stronger neurotoxicity of Aβ42 compared to Aβ40.