SAS-Based Studies of Protein Fibrillation

Carlotta Marasini, Bente Vestergaard

    Abstract

    Protein fibrillation is associated with a number of fatal amyloid diseases (e.g. Alzheimer's and Parkinson's diseases). From a structural point of view, the aggregation process starts from an ensemble of native states that convert into transiently formed oligomers, higher order assemblies and protofibrils and, finally, fibrils. The different species exist in equilibrium in solution leading to a high degree of sample heterogeneity. It is impossible to physically isolate any single species for structural analysis: separation will alter the equilibrium and potentially cause structural changes.Small angle scattering is an optimal method for structural studies of the fibrillation process in order to further the knowledge of the associated diseases. The recorded scattering data include the scattering contribution of all the species in solution and must be decomposed to enable structural modeling of the individual components involved during the fibrillation, notably without physical separation of the species. In this chapter we explain how to optimize a small angle scattering analysis of the fibrillation process and the basic principles behind analysis of the data. We include several practical tips and highlight existing reports, exemplifying the wealth of information that can be derived from the method.

    OriginalsprogEngelsk
    TitelBiological Small Angle Scattering: Techniques, Strategies and Tips
    Antal sider17
    Vol/bind1009
    ForlagSpringer Science+Business Media
    Publikationsdato2017
    Sider149-165
    DOI
    StatusUdgivet - 2017
    NavnAdvances in Experimental Medicine and Biology
    ISSN0065-2598

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