2. Academic Validation
  3. A modular DNA scaffold to study protein-protein interactions at single-molecule resolution

A modular DNA scaffold to study protein-protein interactions at single-molecule resolution

  • Nat Nanotechnol. 2019 Oct;14(10):988-993. doi: 10.1038/s41565-019-0542-7.
Dorota Kostrz 1 2,  Hannah K Wayment-Steele 3,  Jing L Wang 4,  Maryne Follenfant 1,  Vijay S Pande 5,  Terence R Strick 6 7 8,  Charlie Gosse 9 10
Affiliations

Affiliations

  • 1 Ecole Normale Supérieure, Institut de Biologie de l'Ecole Normale Supérieure (IBENS) CNRS, INSERM, PSL Research University, Paris, France.
  • 2 Laboratoire de Photonique et de Nanostructures, LPN-CNRS, Marcoussis, France.
  • 3 Department of Chemistry, Stanford University, Stanford, USA.
  • 4 Institut Jacques Monod, CNRS, Université Paris Diderot, Université de Paris, Paris, France.
  • 5 Department of Bioengineering, Stanford University, Stanford, USA.
  • 6 Ecole Normale Supérieure, Institut de Biologie de l'Ecole Normale Supérieure (IBENS) CNRS, INSERM, PSL Research University, Paris, France. strick@ens.fr.
  • 7 Institut Jacques Monod, CNRS, Université Paris Diderot, Université de Paris, Paris, France. strick@ens.fr.
  • 8 Programme Equipe Labellisée, Ligue Nationale Contre le Cancer, Paris, France. strick@ens.fr.
  • 9 Ecole Normale Supérieure, Institut de Biologie de l'Ecole Normale Supérieure (IBENS) CNRS, INSERM, PSL Research University, Paris, France. gosse@ens.fr.
  • 10 Laboratoire de Photonique et de Nanostructures, LPN-CNRS, Marcoussis, France. gosse@ens.fr.
PMID: 31548690 DOI: 10.1038/s41565-019-0542-7
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z