Unusually broad-spectrum small-molecule sensing using a single protein scaffold
成果类型：
Article
署名作者：
Tian, Hao; Beltran, Jesus; George, Wesley; Lenert-Mondou, Chase; Seder, Norman; Davis, Zoe I.; Swift, Samuel D.; Girke, Thomas; Whitehead, Timothy A.; Wheeldon, Ian; Cutler, Sean R.
署名单位：
University of California System; University of California Riverside; University of California System; University of California Riverside; University of California System; University of California Riverside; University of Colorado System; University of Colorado Boulder; University of California System; University of California Riverside; University of California System; University of California Riverside; University of California System; University of California Riverside
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-8424; 1091-6490
DOI：
10.1073/pnas.2519924122
发表日期：
2025-12-23
页码：
e2519924122
关键词：
biosensors
plant hormone receptors
chemical induced dimerization
synthetic biology
pfas
receptor
perception
EVOLUTION
binding
摘要：
Small-molecule sensing in plants is dominated by chemical-induced dimerization modules. In the abscisic acid (ABA) system, allosteric receptors recruit phosphatase effectors and achieve nM in vivo responses from mu M receptor-ligand interactions. This sensitivity amplification could enable ABA receptors to serve as generic scaffolds for designing small-molecule sensors. To test this, we screened collections of mutant ABA-receptors against 2,726 drugs and other ligands and identified 553 sensors for 6.6% of these ligands. The mutational patterns indicate strong selection for ligand-specific binding pockets. We used these data to develop a sensor design pipeline and isolated sensors for multiple plant natural products, 2,4,6-trinitrotoluene (TNT), and forever per-and polyfluoroalkyl substances (PFAS). Thus, the ABA sensor system enables design and isolation of small-molecule sensors with broad chemical scope and antibody-like simplicity.
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