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

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

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.

• Jezik: Angleški jezik
• Ključne besede: protein aggregation, protein design, synthetic biology
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: 15 str.
• Številčenje: Vol. 14, art. 7973
• UDK: 577
• ISSN pri članku: 2041-1723
• DOI: 10.1038/s41467-023-43742-w
• COBISS.SI-ID: 177039875
• Datum objave v RUL: 25.10.2024

Gradivo je del revije

• Naslov: Nature communications
• Skrajšan naslov: Nat. commun.
• Založnik: Springer Nature
• ISSN: 2041-1723
• COBISS.SI-ID: 2315876

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: biokemija, biopolimeri, biološki procesi, celice, sesalci, simulacije