Topological confinement by a membrane anchor suppresses phase separation into protein aggregates: Implications for prion diseases DOI
Kalpshree Gogte, Fatemeh Mamashli, María Georgina Herrera

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 122(1)

Опубликована: Дек. 31, 2024

Protein misfolding and aggregation are a hallmark of various neurodegenerative disorders. However, the underlying mechanisms driving protein in cellular context incompletely understood. Here, we show that two-dimensional confinement imposed by membrane anchor stabilizes native conformation suppresses liquid-liquid phase separation (LLPS) aggregation. Inherited prion diseases humans neurodegeneration transgenic mice linked to expression anchorless (PrP), suggesting C-terminal glycosylphosphatidylinositol (GPI) PrP impedes spontaneous formation neurotoxic infectious species. Combining unique vitro vivo approaches, demonstrate anchoring membranes prevents LLPS PrP. Upon release from membrane, undergoes conformational transition detergent-insoluble aggregates. Our study demonstrates an essential role GPI preventing

Язык: Английский

Topological confinement by a membrane anchor suppresses phase separation into protein aggregates: Implications for prion diseases DOI
Kalpshree Gogte, Fatemeh Mamashli, María Georgina Herrera

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 122(1)

Опубликована: Дек. 31, 2024

Protein misfolding and aggregation are a hallmark of various neurodegenerative disorders. However, the underlying mechanisms driving protein in cellular context incompletely understood. Here, we show that two-dimensional confinement imposed by membrane anchor stabilizes native conformation suppresses liquid-liquid phase separation (LLPS) aggregation. Inherited prion diseases humans neurodegeneration transgenic mice linked to expression anchorless (PrP), suggesting C-terminal glycosylphosphatidylinositol (GPI) PrP impedes spontaneous formation neurotoxic infectious species. Combining unique vitro vivo approaches, demonstrate anchoring membranes prevents LLPS PrP. Upon release from membrane, undergoes conformational transition detergent-insoluble aggregates. Our study demonstrates an essential role GPI preventing

Язык: Английский

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