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.
![[img]](https://eprints.bbk.ac.uk/style/images/fileicons/text.png) |
Text
Peskett_et_al_combinedManuscript (2).pdf - Author's Accepted Manuscript Restricted to Repository staff only Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (13MB) | Request a copy |
|
|
Text
22241.pdf - Published Version of Record Available under License Creative Commons Attribution. Download (6MB) | Preview |
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 Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Alan Lowe |
| Date Deposited: | 27 Apr 2018 08:46 |
| Last Modified: | 02 Aug 2023 17:41 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/22241 |
Statistics
Additional statistics are available via IRStats2.
Archive Staff Only (login required)
