Assembling membraneless organelles from de novo designed proteins.
Journal
Nature chemistry
ISSN: 1755-4349
Titre abrégé: Nat Chem
Pays: England
ID NLM: 101499734
Informations de publication
Date de publication:
14 Sep 2023
14 Sep 2023
Historique:
received:
22
08
2022
accepted:
09
08
2023
medline:
15
9
2023
pubmed:
15
9
2023
entrez:
14
9
2023
Statut:
aheadofprint
Résumé
Recent advances in de novo protein design have delivered a diversity of discrete de novo protein structures and complexes. A new challenge for the field is to use these designs directly in cells to intervene in biological processes and augment natural systems. The bottom-up design of self-assembled objects such as microcompartments and membraneless organelles is one such challenge. Here we describe the design of genetically encoded polypeptides that form membraneless organelles in Escherichia coli. To do this, we combine de novo α-helical sequences, intrinsically disordered linkers and client proteins in single-polypeptide constructs. We tailor the properties of the helical regions to shift protein assembly from arrested assemblies to dynamic condensates. The designs are characterized in cells and in vitro using biophysical methods and soft-matter physics. Finally, we use the designed polypeptide to co-compartmentalize a functional enzyme pair in E. coli, improving product formation close to the theoretical limit.
Identifiants
pubmed: 37710047
doi: 10.1038/s41557-023-01321-y
pii: 10.1038/s41557-023-01321-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Leverhulme Trust
ID : RGP-2021-049
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/L01386X/1
Organisme : RCUK | Engineering and Physical Sciences Research Council (EPSRC)
ID : EP/K03927X/1
Organisme : Leverhulme Trust
ID : RGP-2021-049
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 795867
Organisme : Leverhulme Trust
ID : RGP-2021-049
Informations de copyright
© 2023. The Author(s).
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