Fichiers

Résumé

The aggregation of proteins is central to many aspects of daily life, including food processing, blood coagulation, eye cataract formation disease and prion-related neurodegenerative infections[1–5]. However, the physical mechanisms responsible for amyloidosis—the irreversible fibril formation of various proteins that is linked to disorders such as Alzheimer’s, Creutzfeldt–Jakob and Huntington’s diseases—have not yet been fully elucidated[6–9]. Here, we show that different stages of amyloid aggregation can be examined by performing a stat- istical polymer physics analysis of single-molecule atomic force microscopy images of heat-denatured b-lactoglobulin fibrils. The atomic force microscopy analysis, supported by theoretical arguments, reveals that the fibrils have a multistranded helical shape with twisted ribbon-like structures. Our results also indicate a possible general model for amyloid fibril assembly and illustrate the potential of this approach for investigating fibrillar systems. 1. Caughey, B. & Lansbury, P. T. Protofibrils, pores, fibrils and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu. Rev. Neurosci. 26, 267–298 (2003). 2. Stradner, A. et al. Equilibrium cluster formation in concentrated protein solutions and colloids. Nature 432, 492–495 (2004). 3. Mezzenga, R., Schurtenberger, P., Burbidge, A. & Michel, M. Understanding foods as soft materials. Nature Mater. 4, 729–740 (2005). 4. Selkoe, D. J. Folding proteins in fatal ways. Nature 426, 900–904 (2003). 5. Chiti, F. & Dobson, C. M. Amyloid formation by globular proteins under native conditions. Nature Chem. Biol. 5, 15–22 (2009). 6. Knowles, T. P. et al. Role of intermolecular forces in defining material properties of protein nanofibrils. Science 318, 1900–1903 (2007). 7. Nelson, R. et al. Structure of the cross-beta spine of amyloid-like fibrils. Nature 435, 773–778 (2005). 8. Chiti, F. & Dobson, C. M. Protein misfolding, functional amyloid and human disease. Annu. Rev. Biochem. 75, 333–366 (2006). 9. Dobson, C. M. Protein folding and misfolding. Nature 426, 884–890 (2003).

Détails

Actions

Aperçu