Maruša Ramšak (Author), Dominique A. Ramirez (Author), Loren E. Hough (Author), Michael R. Shirts (Author), Sara Vidmar (Author), Kristina Eleršič (Author), Gregor Anderluh (Author), Roman Jerala (Author)

Abstract

Membraneless liquid compartments based on phase-separating biopolymers have been observed in diverse cell types and attributed to weak multivalent interactions predominantly based on intrinsically disordered domains. The design of liquid-liquid phase separated (LLPS) condensates based on de novo designed tunable modules that interact in a well-understood, controllable manner could improve our understanding of this phenomenon and enable the introduction of new features. Here we report the construction of CC-LLPS in mammalian cells, based on designed coiled-coil (CC) dimer-forming modules, where the stability of CC pairs, their number, linkers, and sequential arrangement govern the transition between diffuse, liquid and immobile condensates and are corroborated by coarse-grained molecular simulations. Through modular design, we achieve multiple coexisting condensates, chemical regulation of LLPS, condensate fusion, formation from either one or two polypeptide components or LLPS regulation by a third polypeptide chain. These findings provide further insights into the principles underlying LLPS formation and a design platform for controlling biological processes.

Keywords

biokemija;biopolimeri;biološki procesi;celice;sesalci;simulacije;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: KI - National Institute of Chemistry
UDC: 577
COBISS: 177039875 Link will open in a new window
ISSN: 2041-1723
Views: 202
Downloads: 146
Average score: 0 (0 votes)
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Other data

Secondary language: Slovenian
Secondary keywords: biokemija;biopolimeri;biološki procesi;celice;sesalci;simulacije;
Type (COBISS): Article
Pages: str. 1-15
Volume: ǂVol. ǂ14
Issue: article no. 7973
Chronology: 2023
DOI: 10.1038/s41467-023-43742-w
ID: 25381353