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Programmable Allosteric Regulation of Three-Dimensional DNA Nanostructures for Targeted Membrane Protein Degradation.

Zheng Wu,Cuiyan Wu,Kehan Cai,Zhen Huang,Jing Huang,Zhan Wu,Zilong Zhao

Published 2025 in Nano letters (Print)

ABSTRACT

Precise regulation of membrane receptor activity is critical for both basic research and disease management. Here, we present a rational design of a programmable DNA nanostructure capable of precise, reversible, and functional modulation of aptamers in response to specific molecular inputs. The nanostructure allows for programmable and targeted degradation of membrane-associated proteins. By strategically placing an aptamer inside the DNA nanostructure, we achieve effective prevention of aptamer binding toward the target protein. By adding a fuel or anti-fuel strand, the aptamer can be dynamically positioned on either the exterior or interior of the DNA tetrahedron. Importantly, the membrane protein is degraded only when the aptamer lies outside the DNA nanostructure. We demonstrate the potential of allosteric regulation in DNA nanostructures for controlled membrane protein degradation. This allosteric regulation of DNA nanostructures opens a new approach for the manipulation of molecular functions.

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