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The present and the future of protein biosensor engineering
Institution:1. Research School of Chemistry, Australian National University, Canberra, ACT, 2601, Australia;2. Australian Research Council Centre of Excellence in Synthetic Biology, Australian National University, Canberra, ACT 2601, Australia;3. Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, Australian National University, Canberra, ACT 2601, Australia;4. CSIRO Health & Biosecurity, Black Mountain, Canberra, ACT 2600, Australia;5. CSIRO-QUT Synthetic Biology Alliance, Queensland University of Technology, Brisbane, QLD, 4001, Australia;6. Centre for Agriculture and the Bioeconomy, Centre for Genomics and Personalised Health, School of Biology and Environmental Science, Queensland University of Technology, Brisbane, QLD, 4001, Australia;7. Australian Research Council Centre of Excellence in Synthetic Biology, Queensland University of Technology, Brisbane, QLD, 4001, Australia;1. Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China;2. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China;3. Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China;1. Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599, USA;2. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27514, USA
Abstract:Protein biosensors play increasingly important roles in cell and neurobiology and have the potential to revolutionise the way clinical and industrial analytics are performed. The gradual transition from multicomponent biosensors to fully integrated single chain allosteric biosensors has brought the field closer to commercial applications. We evaluate various approaches for converting constitutively active protein reporter domains into analyte operated switches. We discuss the paucity of the natural receptors that undergo conformational changes sufficiently large to control the activity of allosteric reporter domains. This problem can be overcome by constructing artificial versions of such receptors. The design path to such receptors involves the construction of Chemically Induced Dimerisation systems (CIDs) that can be configured to operate single and two-component biosensors.
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