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Programmable de novo designed coiled coil-mediated phase separation in mammalian cells
ID
Ramšak, Maruša
(
Author
),
ID
Ramirez, Dominique A.
(
Author
),
ID
Hough, Loren E.
(
Author
),
ID
Shirts, Michael R.
(
Author
),
ID
Vidmar, Sara
(
Author
),
ID
Eleršič Filipič, Kristina
(
Author
),
ID
Anderluh, Gregor
(
Author
),
ID
Jerala, Roman
(
Author
)
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https://www.nature.com/articles/s41467-023-43742-w
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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.
Language:
English
Keywords:
protein aggregation
,
protein design
,
synthetic biology
Work type:
Article
Typology:
1.01 - Original Scientific Article
Organization:
MF - Faculty of Medicine
Publication status:
Published
Publication version:
Version of Record
Year:
2023
Number of pages:
15 str.
Numbering:
Vol. 14, art. 7973
PID:
20.500.12556/RUL-164452
UDC:
577
ISSN on article:
2041-1723
DOI:
10.1038/s41467-023-43742-w
COBISS.SI-ID:
177039875
Publication date in RUL:
25.10.2024
Views:
120
Downloads:
129
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Record is a part of a journal
Title:
Nature communications
Shortened title:
Nat. commun.
Publisher:
Springer Nature
ISSN:
2041-1723
COBISS.SI-ID:
2315876
Licences
License:
CC BY 4.0, Creative Commons Attribution 4.0 International
Link:
http://creativecommons.org/licenses/by/4.0/
Description:
This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Secondary language
Language:
Slovenian
Keywords:
biokemija
,
biopolimeri
,
biološki procesi
,
celice
,
sesalci
,
simulacije
Projects
Funder:
ARRS - Slovenian Research Agency
Project number:
P4-0176
Name:
Sintezna biologija in imunologija
Funder:
ARRS - Slovenian Research Agency
Project number:
P3-0289
Name:
Značilnosti malignih neoplazem, pomembnih za diagnozo ter napoved poteka bolezni in izida zdravljenja
Funder:
ARRS - Slovenian Research Agency
Project number:
J7-4640
Name:
Inovativna imunoterapija raka preko CAR T celic (CARRS)
Funder:
ARRS - Slovenian Research Agency
Project number:
J1-4406
Name:
CC-Trigger: izpodrivanje proteinskih obvitih vijačnic s pomočjo oprimkov omogoča kinetični nadzor proteinskih sestavov in napredne naprave z več stanji
Funder:
EC - European Commission
Funding programme:
H2020
Project number:
787115
Name:
Molecular machines based on coiled-coil protein origami
Acronym:
MaCChines
Funder:
NIH - National Institutes of Health
Funding programme:
Molecular Biophysics Training Program
Project number:
T32GM065103
Funder:
NSF - National Science Foundation
Funding programme:
Directorate for Biological Sciences
Project number:
1943488
Name:
CAREER: Molecular mechanisms underlying yeast cellular starvation tolerance; spatial reasoning to increase STEM participation
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