Programming conformational cooperativity to regulate allosteric protein-oligonucleotide signal transduction.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 08 2023
14 08 2023
Historique:
received:
13
03
2023
accepted:
03
08
2023
medline:
16
8
2023
pubmed:
15
8
2023
entrez:
14
8
2023
Statut:
epublish
Résumé
Conformational cooperativity is a universal molecular effect mechanism and plays a critical role in signaling pathways. However, it remains a challenge to develop artificial molecular networks regulated by conformational cooperativity, due to the difficulties in programming and controlling multiple structural interactions. Herein, we develop a cooperative strategy by programming multiple conformational signals, rather than chemical signals, to regulate protein-oligonucleotide signal transduction, taking advantage of the programmability of allosteric DNA constructs. We generate a cooperative regulation mechanism, by which increasing the loop lengths at two different structural modules induced the opposite effects manifesting as down- and up-regulation. We implement allosteric logic operations by using two different proteins. Further, in cell culture we demonstrate the feasibility of this strategy to cooperatively regulate gene expression of PLK1 to inhibit tumor cell proliferation, responding to orthogonal protein-signal stimulation. This programmable conformational cooperativity paradigm has potential applications in the related fields.
Identifiants
pubmed: 37580346
doi: 10.1038/s41467-023-40589-z
pii: 10.1038/s41467-023-40589-z
pmc: PMC10425332
doi:
Substances chimiques
Oligonucleotides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4898Informations de copyright
© 2023. Springer Nature Limited.
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