Fibril formation from the amyloid-β peptide is governed by a dynamic equilibrium involving association and dissociation of the monomer

Biophysics Reviews
Masaru Hoshino

Abstract

Here I review the molecular mechanisms by which water-soluble monomeric amyloid-β (Aβ) peptides are transformed into well-organized supramolecular complexes called amyloid fibrils. The mechanism of amyloid formation is considered theoretically on the basis of experimental results, and the structural and mechanistic similarities of amyloid fibrils to three-dimensional crystals are highlighted. A number of important results from the literature are described. These include the observation that a correct ratio of monomer association and dissociation rate constants is key for formation of well-organized amyloid fibrils. The dynamic nature of the amyloid-β structure is discussed, along with the possibly obligate requirement of the transient formation of a hairpin-like fold prior to its incorporation into amyloid fibrils. Many rounds of monomer association and dissociation events may be present during an apparently silent lag-period. Amongst these association/dissociation events, interaction between the C-terminal regions of the Aβ peptide seems to be more favored. Such association and dissociation events occurring in a "trial-and-error" fashion may be an important requirement for the formation of well-organized amyloid fibrils.

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Citations

Mar 3, 2018·International Journal of Molecular Sciences·Farid Rahimi
Mar 22, 2019·Protein Science : a Publication of the Protein Society·Manuel A CastroCharles R Sanders
Jan 9, 2020·Physical Biology·Meng LuGabi Kaminski Schierle
Dec 17, 2020·Chembiochem : a European Journal of Chemical Biology·Chyi Wei Chung, Gabriele S Kaminski Schierle
Nov 5, 2019·Current Opinion in Structural Biology·Rodrigo GallardoSheena E Radford

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Methods Mentioned

BETA
X-ray
NMR
electron microscopy
chemical exchange

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