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Amyloid Proteins pp 209–239Cite as

Noninvasive Structural Analysis of Intermediate Species During Fibrillation: An Application of Small-Angle X-Ray Scattering

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1779))

Abstract

Structural investigation of intermediately formed oligomers and pre-fibrillar species is of tremendous importance in order to elucidate the structural principles of fibrillation, and because intermediate species have been suggested as the pathogenic agents in several amyloid diseases. Structural investigations are however greatly complicated by the dynamic changes between structural states of very different sizes and life-times. Small angle X-ray scattering (SAXS) is an ideal method to handle this challenge. The method provides information about the fibrillation process (number of species present and their volume fractions) and low-resolution 3-dimensional structural models of individual species, notably also of the intermediately formed, in-process species from undisturbed fibrillation equilibria. Here, we provide a detailed description of the methods used for the measurement and analysis of SAXS data from fibrillating samples, exemplified using data from our own research.

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Acknowledgments

The experiences gathered in this chapter were not collected overnight, thus we would like to thank our colleagues and collaborators for significant discussions and help. In particular, we thank current and former members of the BioSAXS group at the University of Copenhagen. From EMBL-Hamburg, we warmly thank Dmitri I. Svergun and several members of his group for highly valuable help throughout this long scientific journey. It is mentioned in particular that the strong commitment of beamline staff is a crucial aspect during this kind of experiments. We greatly acknowledge plenty beamtime at beamlines X33 and P12 (EMBL-Hamburg), without which the development of the methodology described here would not have been possible. We also appreciate funding from The Lundbeck Foundation, the Novo Nordisk Foundation, the Danish Research Council for Health and Disease, and DANSCATT (A.E.L and B.V). This work was additionally supported by SPIN-HD—Chaires d’execellence 2011 from the Agence National de la Recherche, ATIP-Avenir and the French Infrastructure for Integrated Structural Biology (FRISBI—ANR-10-INSB-05-01) to P.B.

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Authors and Affiliations

  1. Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark

    Annette Eva Langkilde, Fátima Herranz-Trillo & Bente Vestergaard

  2. Centre de Biochimie Structurale (CBS), INSERM, CNRS, Universite de Montpellier, Montpellier, France

    Fátima Herranz-Trillo & Pau Bernadó

Authors
  1. Annette Eva Langkilde
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  2. Fátima Herranz-Trillo
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  3. Pau Bernadó
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  4. Bente Vestergaard
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Corresponding author

Correspondence to Bente Vestergaard .

Editor information

Editors and Affiliations

  1. Department of Neuroscience and Physiology, New York University School of Medicine, New York University Langone Health, New York, New York, USA

    Einar M. Sigurdsson

  2. Chronic Disease Programme-CROSADIS CIBERNED, Queen Sofia Foundation, Alzheimer Center CIEN Foundation, Instituto de Salud Carlos III, Madrid, Spain

    Miguel Calero

  3. Institute of Physical Chemistry “Rocasolano”, Spanish National Research Council (CSIC), Madrid, Spain

    María Gasset

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Langkilde, A.E., Herranz-Trillo, F., Bernadó, P., Vestergaard, B. (2018). Noninvasive Structural Analysis of Intermediate Species During Fibrillation: An Application of Small-Angle X-Ray Scattering. In: Sigurdsson, E., Calero, M., Gasset, M. (eds) Amyloid Proteins. Methods in Molecular Biology, vol 1779. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7816-8_14

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  • DOI: https://doi.org/10.1007/978-1-4939-7816-8_14

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7815-1

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