Authors: Dmitry Kurouski, Igor K. Lednev
Addresses: Department of Chemistry, University at Albany, State University of New York, 1400 Washington Ave., Albany, NY 12222, USA. ' Department of Chemistry, University at Albany, State University of New York, 1400 Washington Ave., Albany, NY 12222, USA
Abstract: Amyloid fibrils are associated with many neurodegenerative diseases. Being formed from more than 20 different proteins that are functionally or structurally unrelated, amyloid fibrils share a common cross-β core structure. It is a well-accepted hypothesis that fibril biological activity and the associated toxicity vary with their morphology. Partial denaturation of a native protein usually precedes the initial stage of fibrillation, namely the nucleation process. Low pH and elevated temperature, typical conditions of amyloid fibril formation in vitro, resulted in partial denaturation of the proteins. Cleavage of disulfide bonds results typically in significant disruption of protein native structure and in the formation of the molten global state. Herein we report on a comparative investigation of fibril formation by apo-α-lactalbumin and its analog that contains only one of the four original disulfide bonds using deep UV resonance and non-resonance Raman spectroscopy and atomic force microscopy. Significant differences in the aggregation mechanism and the resulting fibril morphology were found.
Keywords: alpha-lactalbumin; amyloid fibrils; protein disulfide bonds; polymorphism; ultraviolet Raman spectroscopy; Raman spectroscopy; aggregation kinetics; fibrillation kinetics; protein structure; protein aggregation; fibrillation mechanism; neurodegenerative diseases; fibril formation.
International Journal of Biomedical Nanoscience and Nanotechnology, 2011 Vol.2 No.2, pp.167 - 176
Published online: 28 Jun 2011 *Full-text access for editors Access for subscribers Purchase this article Comment on this article