Diverse Structural Conversion and Aggregation Pathways of Alzheimer's Amyloid-beta (1-40)
- Authors
- Lin, Yuxi; Sahoo, Bikash R.; Ozawa, Daisaku; Kinoshita, Misaki; Kang, Juhye; Lim, Mi Hee; Okumura, Masaki; Huh, Yang Hoon; Moon, Eunyoung; Jang, Jae Hyuck; Lee, Hyun-Ju; Ryu, Ka-Young; Ham, Sihyun; Wong, Haing-Sik; Ryu, Kyoung-Seok; Sugiki, Toshihiko; Bang, Jeong Kyu; Hoe, Hyang-Sook; Fujiwara, Toshimichi; Ramamoorthy, Ayyalusamy; Lee, Young-Ho
- Issue Date
- Aug-2019
- Publisher
- AMER CHEMICAL SOC
- Keywords
- Alzheimer' s disease; amyloid beta; amyloid fibril; protein misfolding and aggregation; aggregation pathway; helical structure; phase diagram
- Citation
- ACS NANO, v.13, no.8, pp.8766 - 8783
- Journal Title
- ACS NANO
- Volume
- 13
- Number
- 8
- Start Page
- 8766
- End Page
- 8783
- URI
- http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/676
- DOI
- 10.1021/acsnano.9b01578
- ISSN
- 1936-0851
- Abstract
- Complex amyloid aggregation of amyloid-beta (1-40) (A beta(1-40)) in terms of monomer structures has not been fully understood. Herein, we report the microscopic mechanism and pathways of A beta(1-40) aggregation with macroscopic viewpoints through tuning its initial structure and solubility. Partial helical structures of A beta(1-40) induced by low solvent polarity accelerated cytotoxic A beta(1-40) amyloid fibrillation, while predominantly helical folds did not aggregate. Changes in the solvent polarity caused a rapid formation of beta-structure-rich protofibrils or oligomers via aggregation-prone helical structures. Modulation of the pH and salt concentration transformed oligomers to protofibrils, which proceeded to amyloid formation. We reveal diverse molecular mechanisms underlying A beta(1-40) aggregation with conceptual energy diagrams and propose that aggregation-prone partial helical structures are key to inducing amyloidogenesis. We demonstrate that context-dependent protein aggregation is comprehensively understood using the macroscopic phase diagram, which provides general insights into differentiation of amyloid formation and phase separation from unfolded and folded structures.
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