The interface of condensates of the hnRNPA1 low-complexity domain promotes formation of amyloid fibrils
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Date
2023-10
Publication Type
Journal Article
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yes
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Abstract
The maturation of liquid-like protein condensates into amyloid fibrils has been associated with several neurodegenerative diseases. However, the molecular mechanisms underlying this liquid-to-solid transition have remained largely unclear. Here we analyse the amyloid formation mediated by condensation of the low-complexity domain of hnRNPA1, a protein involved in amyotrophic lateral sclerosis. We show that phase separation and fibrillization are connected but distinct processes that are modulated by different regions of the protein sequence. By monitoring the spatial and temporal evolution of amyloid formation we demonstrate that the formation of fibrils does not occur homogeneously inside the droplets but is promoted at the interface of the condensates. We further show that coating the interface of the droplets with surfactant molecules inhibits fibril formation. Our results reveal that the interface of biomolecular condensates of hnRNPA1 promotes fibril formation, therefore suggesting interfaces as a potential novel therapeutic target against the formation of aberrant amyloids mediated by condensation.
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published
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Journal / series
Volume
15 (10)
Pages / Article No.
1340 - 1349
Publisher
Nature
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Date collected
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Subject
Proteins; Supramolecular assembly
Organisational unit
09572 - Arosio, Paolo / Arosio, Paolo
02891 - ScopeM / ScopeM
03857 - Mezzenga, Raffaele / Mezzenga, Raffaele
Notes
Funding
101002094 - Biologically Inspired Molecular Adhesives towards Multifunctional Biomaterials and Microreactors (EC)
179055 - Protein phase transition: from fundamental biology towards new protein materials (SNF)
179055 - Protein phase transition: from fundamental biology towards new protein materials (SNF)