A Liquid to Solid Phase Transition Underlying Pathological Huntingtin Exon1 Aggregation.
Mol Cell
; 70(4): 588-601.e6, 2018 05 17.
Article
en En
| MEDLINE
| ID: mdl-29754822
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
Enfermedad de Huntington
/
Transición de Fase
/
Agregación Patológica de Proteínas
/
Proteína Huntingtina
Límite:
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2018
Tipo del documento:
Article