UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

A Liquid to Solid Phase Transition Underlying Pathological Huntingtin Exon1 Aggregation

Peskett, TR; Rau, F; O'Driscoll, J; Patani, R; Lowe, AR; Saibil, HR; (2018) A Liquid to Solid Phase Transition Underlying Pathological Huntingtin Exon1 Aggregation. Molecular Cell , 70 (4) 588-601.e6. 10.1016/j.molcel.2018.04.007. Green open access

[img]
Preview
Text
A Liquid to Solid Phase Transition Underlying Pathological Huntingtin Exon1 Aggregation.pdf - Published version

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.

Type: Article
Title: A Liquid to Solid Phase Transition Underlying Pathological Huntingtin Exon1 Aggregation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.molcel.2018.04.007
Publisher version: https://doi.org/10.1016/j.molcel.2018.04.007
Language: English
Additional information: Copyright © 2018 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: huntingtin exon1, aggregation, phase transition, polyQ, electron tomography, fluorescence microscopy
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10047541
Downloads since deposit
80Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item