{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tian H"],"funding":["NSF (NSF)","DOD | ARPA | Defense Sciences Office, DARPA (DSO)","HHS | NIH | National Institute on Aging (NIA)","HHS | NIH | National Institute of General Medical Sciences (NIGMS)"],"pagination":["e2519924122"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12745708"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["122(51)"],"pubmed_abstract":["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 µM 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."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Unusually broad-spectrum small-molecule sensing using a single protein scaffold."],"pmcid":["PMC12745708"],"funding_grant_id":["CERES-D24AC0001","1922642","U19AG023122","MRI-2215705","2128287","2128016","R01-GM151616"],"pubmed_authors":["Girke T","Seder N","Whitehead TA","Tian H","Davis ZI","Swift SD","Lenert-Mondou C","Beltran J","Cutler SR","Wheeldon I","George W"],"additional_accession":[]},"is_claimable":false,"name":"Unusually broad-spectrum small-molecule sensing using a single protein scaffold.","description":"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 µM 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.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-08T05:42:00.465Z","creation":"2026-06-08T03:09:22.621Z"},"accession":"S-EPMC12745708","cross_references":{"pubmed":["41397125"],"doi":["10.1073/pnas.2519924122"]}}