Amino acids modulate liquid-liquid phase separation in vitro and in vivo by regulating protein-protein interactions
OPEN ACCESS
Loading...
Author / Producer
Date
2024-12-10
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
Abstract
Liquid-liquid phase separation (LLPS) is an intracellular process widely used by cells for many key biological functions. It occurs in complex and crowded environments, where amino acids (AAs) are vital components. We have found that AAs render the net interaction between proteins more repulsive. Here, we find that some AAs efficiently suppress LLPS in test tubes (in vitro). We then screen all the proteinogenic AAs and find that three specific AAs, including proline, glutamine, and glycine, significantly suppressed the formation of stress granules (SGs) in U2OS and HeLa cell lines (in vivo) irrespective of stress types. We also observe the effect in primary fibroblast cells, a viable cell model for neurodegenerative disorders. Kinetic studies by live-cell microscopy show that the presence of AAs not only slows down the formation but also decreases the saturating number and prevents the coalescence of SGs. We finally use sedimentation-diffusion equilibrium analytical ultracentrifuge (SE-AUC) to demonstrate that the suppression effects of AAs on LLPS may be due to their modulation in protein-protein and RNA-RNA interactions. Overall, this study reveals an underappreciated role of cellular AAs, which may find biomedical applications, especially in treating SG-associated diseases.
Permanent link
Publication status
published
Editor
Book title
Volume
121 (50)
Pages / Article No.
Publisher
National Academy of Sciences
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
liquid-liquid phase separation; protein-protein interactions; biomolecular condensate; stress granule; amino acid
Organisational unit
09573 - Dufresne, Eric (ehemalig) / Dufresne, Eric (former)
Notes
Funding
202214 - Golgi Physik and Architektur (SNF)