Residue-Specific Dynamics and Local Environmental Changes in Aβ40 Oligomer and Fibril Formation

Angewandte Chemie
Haiyang LiuDeguo Du

Abstract

Elucidating local dynamics of protein aggregation is crucial for understanding the mechanistic details of protein amyloidogenesis. Herein, we studied the residue-specific dynamics and local environmental changes of Aβ40 along the course of aggregation by using para-cyanophenylalanine (PheCN ) as a fluorescent and vibrational probe. Our results show that the PheCN residues introduced at various positions all exhibited an immediate decay of fluorescence intensity, indicating a relatively synergistic process in early oligomer formation. The fast decreases in the fluorescence intensities of residues 19 and 20 in the central hydrophobic core region and residue 10 in the N-terminal region suggest that they play crucial roles in the formation of the oligomeric core. The PheCN 4 residue exhibits a remarkably slower decrease in fluorescence intensity, implicating its dynamic conformational characteristics in oligomer and fibril formation. Our results also suggest that the N-terminal residues in fibrils are surrounded by a relatively hydrophobic local environment, as opposed to being solvated.

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Citations

Jan 10, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Haoqian LiDeguo Du
Jun 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tao ZhangDieter Willbold
Jun 19, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jacob L BouchardTodd M Doran
May 16, 2019·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Liliya VugmeysterRiqiang Fu
Jul 13, 2021·The Journal of Physical Chemistry. B·Clifford MorrisDeguo Du
May 31, 2019·The Journal of Physical Chemistry. B·Achintya KunduMinhaeng Cho

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