Atomic models of de novo designed cc beta-met amyloid-like fibrils

Steinmetz, Michel O, Gattin, Zrinka, Verel, Rene, Ciani, Barbara, Stromer, Thusnelda, Green, Janelle M, Tittmann, Peter, Schulze-Briese, Clemens, Gross, Heinz, van Gunsteren, Wilfred F, Meier, Beat H, Serpell, Louise C, Müller, Shirley A and Kammerer, Richard A (2008) Atomic models of de novo designed cc beta-met amyloid-like fibrils. Journal of Molecular Biology, 376 (3). pp. 898-912. ISSN 0022-2836

Full text not available from this repository.

Abstract

The common characteristics of amyloid and amyloid-like fibrils from disease- and non-disease-associated proteins offer the prospect that well-defined model systems can be used to systematically dissect the driving forces of amyloid formation. We recently reported the de novo designed cc peptide model system that forms a native-like coiled-coil structure at low temperatures and which can be switched to amyloid-like fibrils by increasing the temperature. Here, we report a detailed molecular description of the system in its fibrillar state by characterizing the cc beta-Met variant using several microscopic techniques, circular dichroism spectroscopy, X-ray fiber diffraction, solid-state nuclear magnetic resonance, and molecular dynamics calculations. We show that cc beta-Met forms amyloid-like fibrils of different morphologies on both the macroscopic and atomic levels, which can be controlled by variations of assembly conditions. Interestingly, heterogeneity is also observed along single fibrils. We propose atomic models of the cc beta-Met amyloid-like fibril, which are in good agreement with all experimental data. The models provide a rational, explanation why oxidation of methionine residues completely abolishes cc beta-Met amyloid fibril formation, indicating that a small number of site-specific hydrophobic interactions can play a major role in the packing of polypeptide-chain segments within amyloid fibrils. The detailed structural information available for the cc beta model system provides a strong molecular basis for understanding the influence and relative contribution of hydrophobic interactions on native-state stability, kinetics of fibril formation, fibril packing, and polymorphism. (C) 2007 Elsevier Ltd. All rights reserved.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: EPrints Services
Date Deposited: 06 Feb 2012 21:09
Last Modified: 30 Nov 2012 17:09
URI: http://sro.sussex.ac.uk/id/eprint/29875
📧 Request an update