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

Autor: Liu H; Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA., Morris C; Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA., Lantz R; Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA., Kent TW; Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA., Elbassal EA; Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA., Wojcikiewicz EP; Department of Biomedical Science, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA., Du D; Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2018 Jul 02; Vol. 57 (27), pp. 8017-8021. Date of Electronic Publication: 2018 Jun 14.
DOI: 10.1002/anie.201802490
Abstrakt: 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.
(© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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