A single-component, light-assisted uncaging switch for endoproteolytic release

Mingguang Cui, Seunghwan Lee, Sung Hwan Ban, Jae Ryun Ryu, Meiying Shen, Soo Hyun Yang, Jin Young Kim, Seul Ki Choi, Jaemin Han, Yoonhee Kim, Kihoon Han, Donghun Lee, Woong Sun, Hyung Bae Kwon, Dongmin Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Proteases function as pivotal molecular switches, initiating numerous biological events. Notably, potyviral protease, derived from plant viruses, has emerged as a trusted proteolytic switch in synthetic biological circuits. To harness their capabilities, we have developed a single-component photocleavable switch, termed LAUNCHER (Light-Assisted UNcaging switCH for Endoproteolytic Release), by employing a circularly permutated tobacco etch virus protease and a blue-light-gated substrate, which are connected by fine-tuned intermodular linkers. As a single-component system, LAUNCHER exhibits a superior signal-to-noise ratio compared with multi-component systems, enabling precise and user-controllable release of payloads. This characteristic renders LAUNCHER highly suitable for diverse cellular applications, including transgene expression, tailored subcellular translocation and optochemogenetics. Additionally, the plug-and-play integration of LAUNCHER into existing synthetic circuits facilitates the enhancement of circuit performance. The demonstrated efficacy of LAUNCHER in improving existing circuitry underscores its significant potential for expanding its utilization in various applications. (Figure presented.)

Original languageEnglish
Pages (from-to)353-364
Number of pages12
JournalNature Chemical Biology
Volume20
Issue number3
DOIs
Publication statusPublished - 2024 Mar

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2023.

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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