Cell
Volume 153, Issue 7, 20 June 2013, Pages 1602-1611
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A Bilirubin-Inducible Fluorescent Protein from Eel Muscle

https://doi.org/10.1016/j.cell.2013.05.038Get rights and content
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Highlights

  • A novel eel fluorescent protein UnaG belongs to the fatty-acid-binding protein family

  • UnaG fluorescence is induced by a noncovalent ligand, bilirubin, a heme metabolite

  • The HoloUnaG crystal structure at 1.2 Å revealed a biplanar coordination of bilirubin

  • UnaG enabled the establishment of a human bilirubin assay with clinical application

Summary

The fluorescent protein toolbox has revolutionized experimental biology. Despite this advance, no fluorescent proteins have been identified from vertebrates, nor has chromogenic ligand-inducible activation or clinical utility been demonstrated. Here, we report the cloning and characterization of UnaG, a fluorescent protein from Japanese eel. UnaG belongs to the fatty-acid-binding protein (FABP) family, and expression in eel is restricted to small-diameter muscle fibers. On heterologous expression in cell lines or mouse brain, UnaG produces oxygen-independent green fluorescence. Remarkably, UnaG fluorescence is triggered by an endogenous ligand, bilirubin, a membrane-permeable heme metabolite and clinical health biomarker. The holoUnaG structure at 1.2 Å revealed a biplanar coordination of bilirubin by reversible π-conjugation, and we used this high-affinity and high-specificity interaction to establish a fluorescence-based human bilirubin assay with promising clinical utility. UnaG will be the prototype for a versatile class of ligand-activated fluorescent proteins, with applications in research, medicine, and bioengineering.

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