Early Events in The Fibrillation of Monomeric Insulin
Document Type
Article
Publication Date
2005
Digital Object Identifier (DOI)
https://doi.org/10.1074/jbc.M504298200
Abstract
Insulin has a largely α-helical structure and exists as a mixture of hexameric, dimeric, and monomeric states in solution, depending on the conditions: the protein is monomeric in 20% acetic acid. Insulin forms amyloid-like fibrils under a variety of conditions, especially at low pH. In this study we investigated the fibrillation of monomeric human insulin by monitoring changes in CD, attenuated total reflectance-Fourier transform infrared spectroscopy, 8-anilinonaphthalenesulfonic acid fluorescence, thioflavin T fluorescence, dynamic light scattering, and H/D exchange during the initial stages of the fibrillation process to provide insight into early events involving the monomer. The results demonstrate the existence of structural changes occurring before the onset of fibril formation, which are detectable by multiple probes. The data indicate at least two major populations of oligomeric intermediates between the native monomer and fibrils. Both have significantly non-native conformations, and indicate that fibrillation occurs from a betarich structure significantly distinct from the native fold.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Journal of Biological Chemistry, v. 280, issue 52, p. 42669-42675
Scholar Commons Citation
Ahmad, Atta; Uversky, Vladimir N.; Hong, Dongpyo; and Fink, Anthony L., "Early Events in The Fibrillation of Monomeric Insulin" (2005). Molecular Medicine Faculty Publications. 753.
https://digitalcommons.usf.edu/mme_facpub/753
