Conformational Constraints for Amyloid Fibrillation: The Importance of Being Unfolded
Fibrillation, Partially Folded Intermediate, Conformational Stability, Natively Unfolded Protein, Amyloid
Digital Object Identifier (DOI)
Recent reports give strong support to the idea that amyloid fibril formation and the subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins. In this review, recent findings are surveyed to illustrate that protein fibrillogenesis requires a partially folded conformation. This amyloidogenic conformation is relatively unfolded, and shares many structural properties with the pre-molten globule state, a partially folded intermediate frequently observed in the early stages of protein folding and under some equilibrium conditions. The inherent flexibility of such an intermediate is essential in allowing the conformational rearrangements necessary to form the core cross-beta structure of the amyloid fibril.
Was this content written or created while at USF?
Citation / Publisher Attribution
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, v. 1698, issue 2, p. 131-153
Scholar Commons Citation
Uversky, Vladimir N. and Fink, Anthony L., "Conformational Constraints for Amyloid Fibrillation: The Importance of Being Unfolded" (2004). Molecular Medicine Faculty Publications. 725.