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Residue‐Specific Dynamics and Local Environmental Changes in Aβ40 Oligomer and Fibril Formation
Author(s) -
Liu Haiyang,
Morris Clifford,
Lantz Richard,
Kent Thomas W.,
Elbassal Esmail A.,
Wojcikiewicz Ewa P.,
Du Deguo
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201802490
Subject(s) - oligomer , chemistry , residue (chemistry) , fluorescence , fibril , molecular dynamics , biophysics , protein aggregation , protein structure , crystallography , biochemistry , organic chemistry , computational chemistry , physics , quantum mechanics , biology
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 (Phe CN ) as a fluorescent and vibrational probe. Our results show that the Phe CN 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 Phe CN 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.