Location and Concentration of Aromatic-Rich Segments Dictates the Percolating Inter-Molecular Network and Viscoelastic Properties of Ageing Condensates.

ABSTRACT: Maturation of functional liquid-like biomolecular condensates into solid-like aggregates has been linked to the onset of several neurodegenerative disorders. Low-complexity aromatic-rich kinked segments (LARKS) contained in numerous RNA-binding proteins can promote aggregation by forming inter-protein β-sheet fibrils that accumulate over time and ultimately drive the liquid-to-solid transition of the condensates. Here, atomistic molecular dynamics simulations are combined with sequence-dependent coarse-grained models of various resolutions to investigate the role of LARKS abundance and position within the amino acid sequence in the maturation of condensates. Remarkably, proteins with tail-located LARKS display much higher viscosity over time than those in which the LARKS are placed toward

SUBMITTER: Blazquez S 

PROVIDER: S-EPMC10477902 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature