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    A liquid to solid phase transition underlying pathological huntingtin exon1 aggregation

    Peskett, T.R. and Rau, F. and O'Driscoll, Jonathan and Patani, R and Lowe, Alan R. and Saibil, Helen R. (2018) A liquid to solid phase transition underlying pathological huntingtin exon1 aggregation. Molecular Cell 7 (4), P588-601.E6. ISSN 1097-2765.

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    Abstract

    Huntington’s disease is caused by an abnormally long polyglutamine tract in the huntingtin protein. This leads to the generation and deposition of N-terminal exon1 fragments of the protein in intracellular aggregates. We combined electron tomography and quantitative fluorescence microscopy to analyze the structural and material properties of huntingtin exon1 assemblies in mammalian cells, in yeast, and in vitro. We found that huntingtin exon1 proteins can form reversible liquid-like assemblies, a process driven by huntingtin’s polyQ tract and proline-rich region. In cells and in vitro, the liquid-like assemblies converted to solid-like assemblies with a fibrillar structure. Intracellular phase transitions of polyglutamine proteins could play a role in initiating irreversible pathological aggregation.

    Metadata

    Item Type: Article
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Research Centre: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Alan Lowe
    Date Deposited: 27 Apr 2018 08:46
    Last Modified: 27 Jan 2020 08:14
    URI: http://eprints.bbk.ac.uk/id/eprint/22241

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