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AFM study of glucagon fibrillation via oligomeric structures resulting in interwoven fibrils

Dong, Mingdong and Bruun Hovgaard, Mads and Xu, Sailong and Otzen, Daniel Erik and Besenbacher, Flemming (2006) AFM study of glucagon fibrillation via oligomeric structures resulting in interwoven fibrils. Nanotechnology, 17 (16). pp. 4003-4009. ISSN 09574484

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Official URL: http://dx.doi.org/10.1088/0957-4484/17/16/001

Abstract

Glucagon is a 29-residue amphiphatic hormone involved in the regulation of blood glucose levels in conjunction with insulin. In concentrated aqueous solutions, glucagon spontaneously aggregates to form amyloid fibrils,destroying its biological activity. In this study we utilize the atomic force microscope (AFM) to elucidate the fibrillation mechanism of glucagon at the nanoscale under acidic conditions (pH 2.0) by visualizing the nanostructures of fibrils formed at different stages of the incubation. Hollow disc-shaped oligomers form at an early stage in the process and subsequently rearrange to more solid oligomers. These oligomers co-exist with, and most likely act as precursors for, protofibrils, which subsequently associate to form at least three different classes of higher-order fibrils of different heights. A repeat unit of around 50 nm along the main fibril axis suggests a helical arrangement of interwoven protofibrils. The diversity of oligomeric and fibrillar arrangements formed at pH 2.0 complements previous spectroscopic analyses that revealed that fibrils formed under different conditions can differ substantially in stability and secondary structure.

Item Type:Article
Subjects:Analytical Science > Microscopy and probe methods
Biomedical Science > Nanobiotechnology
Biomedical Science > Nanotechnology for human health
ID Code:177
Deposited By:Lesley Tobin
Deposited On:13 Nov 2008 10:46
Last Modified:27 Jan 2009 16:14

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