Uncovering Intermolecular Interactions Driving the Liquid-Liquid Phase Separation of the TDP-43 Low-Complexity Domain via Atomistic Dimerization Simulations.

ABSTRACT: Liquid-liquid phase separation (LLPS) of transactive response DNA-binding protein of 43 kDa (TDP-43), which exerts multiple functions in the splicing, trafficking, and stabilization of RNA, mediates the formation of membraneless condensates with crucial physiological roles, while its aberrant LLPS is linked to multiple neurodegenerative diseases. However, due to the heterogeneous and dynamic nature of LLPS, major gaps remain in understanding the precise intermolecular interactions driving LLPS and how specific mutations alter LLPS dynamics. Here, we investigated the molecular mechanisms underlying the LLPS of the TDP-43 low-complexity domain (LCD) by simulating the dimerization process using all-atom discrete molecular dynamics with microsecond-long simulations. Our results showed that the

SUBMITTER: Tang H 

PROVIDER: S-EPMC11590498 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature