{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:57:37Z","timestamp":1790927857234,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001793","name":"Queensland University of Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001793","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chemically induced protein dimerisation (CID) is a widely used approach for detecting and actuating small\u2010molecule\u2010protein interactions. Here, we demonstrate that CID systems can be used as building blocks for higher\u2010order ligand\u2010controlled protein systems. To this end, we converted classical FK506\u2010 and cyclosporine A\u2010controlled CIDs into single\u2010chain pseudo\u2010allosteric proteins. These systems displayed 15\u2010 and 50\u2010fold gains in ligand affinity compared with the parental components operating in trans. Using these fusion proteins as baits in mRNA display, we identified FN3con binding domains that recognise the holo state of each bait with subnanomolar affinity and &gt;100\u2010fold selectivity over the apo form. Integration of the binding domains and intramolecular CIDs into two\u2010component enzymatic protein biosensors enabled quantification of the cognate ligands with low\u2010nanomolar limits of detection (LODs). ELISA assays based on the developed systems displayed mid\u2010picomolar LODs and accurately quantified FK506 and cyclosporine A in unprocessed blood samples from transplant patients with accuracy comparable to that of LC\u2010MS\/MS. This work establishes a generalisable strategy for harnessing the affinity gains of intramolecular CID systems to create gain\u2010of\u2010signal assays for small molecules and ions.<\/jats:p>","DOI":"10.1002\/anie.9707369","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:48:01Z","timestamp":1790927281000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Conformation\u2010Selective Binding Domains of Intramolecular Chemically Induced Protein Dimerisation Systems"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5664-8303","authenticated-orcid":false,"given":"Zhenling","family":"Cui","sequence":"first","affiliation":[{"name":"ARC Centre of Excellence in Synthetic Biology  Brisbane Queensland Australia"},{"name":"Centre For Agriculture and the Bioeconomy Queensland University of Technology  Brisbane Queensland Australia"},{"name":"School of Biology and 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