crowding alone cannot account for cosolute effect on amyloid aggregation拥挤无法占cosolute影响淀粉样蛋白聚合.pdfVIP

Crowding Alone Cannot Account for Cosolute Effect on Amyloid Aggregation 1,2 1,2 3 3,4 1 1,2 Shahar Sukenik , Regina Politi , Lior Ziserman , Dganit Danino , Assaf Friedler , Daniel Harries * 1 Institute of Chemistry, The Fritz Haber Research Center, The Hebrew University of Jerusalem, Edmund J. Safra Campus, Jerusalem, Israel, 2 The Fritz Haber Research Center, The Hebrew University of Jerusalem, Edmund J. Safra Campus, Jerusalem, Israel, 3 Department of Biotechnology and Food Engineering, The Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa, Israel, 4 The Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa, Israel Abstract Amyloid fiber formation is a specific form of protein aggregation, often resulting from the misfolding of native proteins. Aimed at modeling the crowded environment of the cell, recent experiments showed a reduction in fibrillation halftimes for amyloid-forming peptides in the presence of cosolutes that are preferentially excluded from proteins and peptides. The effect of excluded cosolutes has previously been attributed to the large volume excluded by such inert cellular solutes, sometimes termed ‘‘macromolecular crowding’’. Here, we studied a model peptide that can fold to a stable monomeric b- hairpin conformation, but under certain solution conditions aggregates in the form of amyloid fibrils. Using Circular Dichroism spectroscopy (CD), we found that, in the presence of polyols and polyethylene glycols acting as excluded cosolutes, the monomeric b-hairpin conformation was stabilized with respect