20.500.12556/RUL-164452 Programmable de novo designed coiled coil-mediated phase separation in mammalian cells 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. protein aggregation protein design synthetic biology biokemija biopolimeri biološki procesi celice sesalci simulacije true false true Angleški jezik Slovenski jezik Članek v reviji 2024-10-25 11:58:21 2024-10-25 11:58:22 2025-03-10 11:36:09 0000-00-00 00:00:00 2023 0 0 15 str. art. 7973 Vol. 14 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577 2041-1723 10.1038/s41467-023-43742-w 177039875 s41467-023-43742-w_(1).pdf s41467-023-43742-w_(1).pdf 1 69231BC4CB8E3BA67C68476E3B41EFA1 744a237dead619a561652fe856ae358fc73f7520e3d2a3038f2903b693493866 995d9b26-92b7-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=194861 https://www.nature.com/articles/s41467-023-43742-w 0 a706328b-a7ef-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=195983 Medicinska fakulteta 0 0 0