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Dorota Kostrz

Post doctorante financée par le LabEx MemoLife.


A modular DNA scaffold to study protein–protein interactions at single-molecule resolution.
Kostrz D, Wayment-Steele HK, Wang JL, Follenfant M, Pande VS, Strick TR, Gosse C.

Abstract

The residence time of a drug on its target has been suggested as a more pertinent metric of therapeutic efficacy than the traditionally used affinity constant. Here, we introduce junctured-DNA tweezers as a generic platform that enables real-time observation, at the single-molecule level, of biomolecular interactions. This tool corresponds to a double-strand DNA scaffold that can be nanomanipulated and on which proteins of interest can be engrafted thanks to widely used genetic tagging strategies. Thus, junctured-DNA tweezers allow a straightforward and robust access to single-molecule force spectroscopy in drug discovery, and more generally in biophysics. Proof-of-principle experiments are provided for the rapamycin-mediated association between FKBP12 and FRB, a system relevant in both medicine and chemical biology. Individual interactions were monitored under a range of applied forces and temperatures, yielding after analysis the characteristic features of the energy profile along the dissociation landscape.

More information
CNRS press release


Nat Nanotechnol. 2019 Sep 23. doi : 10.1038/s41565-019-0542-7