Formation of Amyloid Fibrils In Vitro from Partially Unfolded Intermediates of Human γC-Crystallin

Abstract

HgammaC-Crys formed amyloid fibrils on incubation at low pH via a partially unfolded intermediate. This process could contribute to the early stages of the formation of light-scattering species in the eye lens.

Structural Changes in Amelogenin upon Self-assembly and Mineral Interactions

“…Furthermore, it has been reported that amyloid fibril assembly occurs via unfolded or partially folded intermediates, containing large portions of PPII and random coil domains (Booth et al, 1997;Wang et al, 2010). Interestingly, our recent cryoEM studies demonstrated that amelogenin assembly occurs in a stepwise hierarchical process via oligomeric intermediates (Fang et al, 2011a,b).…”

Resolution of localized small molecule–Aβ interactions by deep-ultraviolet resonance Raman spectroscopy

“…UVRR has been employed previously to characterize the core structure in Aβ(1-40) fibrils [56], as well as the fibrillization of other amyloidogenic peptides and proteins [57][58][59][60][61]. The UVRR spectrum of LMW Aβ(1-42) is visually similar to other disordered homo-polypeptides (Fig.…”

Congenital Cataract-Causing Mutation G129C in γC-Crystallin Promotes the Accumulation of Two Distinct Unfolding Intermediates That Form Highly Toxic Aggregates

“…It is worth noting that mutations in some of the crystallin genes have been associated with non-cataract abnormities such as neurodegenerative diseases, cardiomyopathy, tumorigenesis and retinal and vascular disorders [23][24][25][26]. Similar to proteins involved in neurodegenerative diseases, crystallins can also form amyloidlike fibrils under certain solution conditions [27][28][29][30][31][32][33]. However, the consequence of crystallin fibrillization in cataract formation, as well as in non-lens disorders, remains elusive since amorphous aggregates but not amyloid fibrils dominate the water-insoluble protein fractions isolated from cataractous lenses [3].…”