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Liquid-liquid phase separation of tau protein: The crucial role of electrostatic interactions.

ABSTRACT: Recent studies have indicated that tau, a protein involved in Alzheimer's disease and other neurodegenerative disorders, has a propensity to undergo liquid-liquid phase separation (LLPS). However, the mechanism of this process remains unknown. Here, we demonstrate that tau LLPS is largely driven by intermolecular electrostatic interactions between the negatively charged N-terminal and positively charged middle/C-terminal regions, whereas hydrophobic interactions play a surprisingly small role. Furthermore, our results reveal that, in contrast to previous suggestions, phosphorylation is not required for tau LLPS. These findings provide a foundation for understanding the mechanism by which phosphorylation and other posttranslational modifications could modulate tau LLPS in the context of specific physiological functions as well as pathological interactions.

SUBMITTER: Boyko S

PROVIDER: S-EPMC6643045 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Liquid-liquid phase separation of tau protein: The crucial role of electrostatic interactions.

Boyko Solomiia S Qi Xu X Chen Tien-Hao TH Surewicz Krystyna K Surewicz Witold K WK

The Journal of biological chemistry 20190516 29

Recent studies have indicated that tau, a protein involved in Alzheimer's disease and other neurodegenerative disorders, has a propensity to undergo liquid-liquid phase separation (LLPS). However, the mechanism of this process remains unknown. Here, we demonstrate that tau LLPS is largely driven by intermolecular electrostatic interactions between the negatively charged N-terminal and positively charged middle/C-terminal regions, whereas hydrophobic interactions play a surprisingly small role. F ...[more]

PMID: 31097543

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