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DNA-Regulated Multi-Protein Complement Control.

Authors :
Ma Y
Winegar PH
Figg CA
Ramani N
Anderson AJ
Ngo K
Ahrens JF
Chellam NS
Kim YJ
Mirkin CA
Source :
Journal of the American Chemical Society [J Am Chem Soc] 2024 Dec 04; Vol. 146 (48), pp. 32912-32918. Date of Electronic Publication: 2024 Nov 21.
Publication Year :
2024

Abstract

In nature, the interactions between proteins and their complements/substrates can dictate complex functions. Herein, we explore how DNA on nucleic acid modified proteins can be used as scaffolds to deliberately control interactions with a peptide complement (by adjusting length, sequence, and rigidity). As model systems, split GFPs were covalently connected through DNA scaffolds (36-58 bp). Increasing the length or decreasing the rigidity of the DNA scaffold (through removal of the duplex) increases the extent of intramolecular protein binding (up to 7.5-fold) between these GFP fragments. Independent and dynamic control over functional outputs can also be regulated by DNA hybridization; a multi-protein (split CFP and YFP) architecture was synthesized and characterized by fluorescence. This ternary construct shows that DNA displacement strands in different stoichiometric ratios can be used deliberately to regulate competitive binding between two unique sets of proteins. These studies establish a foundation for creating new classes of biological machinery based upon the concept of DNA-regulated multi-protein complement control.

Details

Language :
English
ISSN :
1520-5126
Volume :
146
Issue :
48
Database :
MEDLINE
Journal :
Journal of the American Chemical Society
Publication Type :
Academic Journal
Accession number :
39569872
Full Text :
https://doi.org/10.1021/jacs.4c11315