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A rational blueprint for the design of chemically-controlled protein switches

Biology

A rational blueprint for the design of chemically-controlled protein switches

S. Shui, P. Gainza, et al.

Discover an innovative computational protein design strategy that transforms drug-inhibited protein interactions into functional OFF- and ON-switches, enhancing cellular activities in synthetic circuits. This exciting research was conducted by Sailan Shui, Pablo Gainza, Leo Scheller, Che Yang, Yoichi Kurumida, Stéphane Rosset, Sandrine Georgeon, Raphaël B. Di Roberto, Rocío Castellanos-Rueda, Sai T. Reddy, and Bruno E. Correia.

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Playback language: English
Abstract
Small-molecule responsive protein switches are crucial for controlling synthetic cellular activities. This paper presents a computational protein design strategy to repurpose drug-inhibited protein-protein interactions as OFF- and ON-switches. Chemically-disruptable heterodimers (CDHs) and activation by inhibitor release switches (AIRs) were designed and shown to effectively control synthetic circuits in mammalian cells, expanding the chemical space and logic responses in living cells.
Publisher
Nature Communications
Published On
Oct 01, 2021
Authors
Sailan Shui, Pablo Gainza, Leo Scheller, Che Yang, Yoichi Kurumida, Stéphane Rosset, Sandrine Georgeon, Raphaël B. Di Roberto, Rocío Castellanos-Rueda, Sai T. Reddy, Bruno E. Correia
Tags
small-molecule switches
protein-protein interactions
synthetic circuits
mammalian cells
protein design
chemically-disruptable heterodimers
inhibitor release

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