Structural highlights
Publication Abstract from PubMedMotivated by the growing recognition of citrate as a central metabolite in a variety of biological processes associated with healthy and diseased cellular states, we have developed a series of high-performance genetically encoded citrate biosensors suitable for imaging of citrate concentrations in mammalian cells. The design of these biosensors was guided by structural studies of the citrate-responsive sensor histidine kinase and took advantage of the same conformational changes proposed to propagate from the binding domain to the catalytic domain. Following extensive engineering based on a combination of structure guided mutagenesis and directed evolution, we produced an inverse-response biosensor (DeltaF/F min approximately 18) designated Citroff1 and a direct-response biosensor (DeltaF/F min approximately 9) designated Citron1. We report the X-ray crystal structure of Citron1 and demonstrate the utility of both biosensors for qualitative and quantitative imaging of steady-state and pharmacologically perturbed citrate concentrations in live cells. High-Performance Intensiometric Direct- and Inverse-Response Genetically Encoded Biosensors for Citrate.,Zhao Y, Shen Y, Wen Y, Campbell RE ACS Cent Sci. 2020 Aug 26;6(8):1441-1450. doi: 10.1021/acscentsci.0c00518. Epub, 2020 Jul 9. PMID:32875085[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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