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Supersaturation, a Critical Factor Underlying Proteostasis of Amyloid Fibril Formation.

Authors :
Goto, Yuji
Nakajima, Kichitaro
Yamamoto, Suguru
Yamaguchi, Keiichi
Source :
Journal of Molecular Biology. Jul2024, Vol. 436 Issue 14, pN.PAG-N.PAG. 1p.
Publication Year :
2024

Abstract

Solubility- and supersaturation-limited crystallization and amyloid fibril formation. The cycle of crystallization and dissolution of sodium acetate suggests the formation and dissolution cycle of amyloid fibrils. AFM image of β2-microglobulin amyloid fibrils was modified from Katou et al. Protein Sci. 11(9) (2002) 2218–2229. [Display omitted] • Supersaturation is required for the formation of crystal-like amyloid fibrils. • Breakdown of supersaturation triggers amyloid formation and onset of amyloidosis. • Supersaturation-dependent coupled equilibrium links unfolding and amyloid formation. • Preventing amyloid ignition will be more effective than extinguishing amyloid fire. • Healthy proteostasis involves factors retaining supersaturation of amyloid proteins. From a physicochemical viewpoint, amyloid fibril formation is a phase transition from soluble to crystal-like sates limited by supersaturation. It occurs only above solubility (i.e., the solubility limit) coupled with a breakdown of supersaturation. Although many studies have examined the role of molecular chaperones in the context of proteostasis, the role of supersaturation has not been addressed. Moreover, although molecular chaperone-dependent disaggregations have been reported for preformed amyloid fibrils, amyloid fibrils will not dissolve above the solubility of monomers, even if agitations fragment long fibrils to shorter amyloid particles. On the other hand, on considering a reversible and coupled equilibrium of interactions, folding/unfolding and amyloid formation/disaggregation, molecules stabilizing native states can work as a disaggregase reversing the amyloid fibrils to monomers. It is likely that the proteostasis network has various intra- and extracellular components which disaggregate preformed amyloid fibrils as well as prevent amyloid formation. Further studies with a view of solubility and supersaturation will be essential for comprehensive understanding of proteostasis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00222836
Volume :
436
Issue :
14
Database :
Academic Search Index
Journal :
Journal of Molecular Biology
Publication Type :
Academic Journal
Accession number :
178069917
Full Text :
https://doi.org/10.1016/j.jmb.2024.168475