Programmable de novo designed coiled coil-mediated phase separation in mammalian cells.

Autor: Ramšak M; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.; Interdisciplinary doctoral study of biomedicine, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia., Ramirez DA; Department of Biochemistry, University of Colorado Boulder, Boulder, CO, USA., Hough LE; Department of Physics and BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, USA., Shirts MR; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, USA., Vidmar S; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.; Interdisciplinary doctoral study of biomedicine, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia., Eleršič Filipič K; Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, Slovenia., Anderluh G; Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, Slovenia., Jerala R; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia. roman.jerala@ki.si.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Dec 02; Vol. 14 (1), pp. 7973. Date of Electronic Publication: 2023 Dec 02.
DOI: 10.1038/s41467-023-43742-w
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: