Driving amyloid toxicity in a yeast model by structural changes: a molecular approach

作者：Berthelot Karine; Immel Francoise; Gean Julie; Lecomte Sophie; Oda Reiko; Kauffmann Brice; Cullin Christophe^*

来源：The FASEB Journal, 2009, 23(7): 2254-2263.

DOI：10.1096/fj.08-125724

• aggregation
• FTIR
• folding

The amyloid aggregation pathway is a multistep process, and many in vitro studies have highlighted the role of particular intermediates in the cellular toxicity of various amyloid diseases. In a previous study, we generated a yeast toxic mutant (M8) of the harmless model amyloid protein Het-s(218-289). In this study, we compared the aggregation characteristics of the wild-type (WT) and the toxic mutant at the molecular level. Both proteins formed fibrillar amyloid aggregates but with different dye-binding properties and X-ray diffraction patterns. The toxic amyloid formed very unusual short (80 nm) unbranched fibers visible on transmission electron microscopy. Fourier transform infrared spectroscopy demonstrated that M8 beta-sheets were essentially organized into a mixed parallel and antiparallel structure, whereas the WT protein displayed a predominantly parallel organization. Cellular toxicity may therefore be related to assembly of the toxic amyloid in a new aggregation pathway.-Berthelot, K., Immel, F., Gean, J., Lecomte, S., Oda, R., Kauffmann, B., Cullin, C. Driving amyloid toxicity in a yeast model by structural changes: a molecular approach. FASEB J. 23, 2254-2263 (2009)

• 出版日期2009-7