Amyloidogenesis of Natively Unfolded Proteins
Document Type
Article
Publication Date
2008
Keywords
Amyloid Fibril, Fibrillation, Amyloidogenesis, Conformational Disease, Partially Folded Conformation, Natively Unfolded Protein, Intrinsically Disordered Protein
Digital Object Identifier (DOI)
http://dx.doi.org/10.2174/156720508784533312
Abstract
Aggregation and subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins. The accumulated data support the model where protein fibrillogenesis proceeds via the formation of a relatively unfolded amyloidogenic conformation, which shares many structural properties with the pre-molten globule state, a partially folded intermediate first found during the equilibrium and kinetic (un)folding studies of several globular proteins and later described as one of the structural forms of natively unfolded proteins. The flexibility of this structural form is essential for the conformational rearrangements driving the formation of the core cross-beta structure of the amyloid fibril. Obviously, molecular mechanisms describing amyloidogenesis of ordered and natively unfolded proteins are different. For ordered protein to fibrillate, its unique and rigid structure has to be destabilized and partially unfolded. On the other hand, fibrillogenesis of a natively unfolded protein involves the formation of partially folded conformation; i.e., partial folding rather than unfolding. In this review recent findings are surveyed to illustrate some unique features of the natively unfolded proteins amyloidogenesis.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Current Alzheimer Research, v. 5, issue 3, p. 260-287
Scholar Commons Citation
Uversky, Vladimir N., "Amyloidogenesis of Natively Unfolded Proteins" (2008). Molecular Medicine Faculty Publications. 792.
https://digitalcommons.usf.edu/mme_facpub/792
