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Photochemistry of flavoprotein light sensors

Abstract

Three major classes of flavin photosensors, light oxygen voltage (LOV) domains, blue light sensor using FAD (BLUF) proteins and cryptochromes (CRYs), regulate diverse biological activities in response to blue light. Recent studies of structure, spectroscopy and chemical mechanism have provided unprecedented insight into how each family operates at the molecular level. In general, the photoexcitation of the flavin cofactor leads to changes in redox and protonation states that ultimately remodel protein conformation and molecular interactions. For LOV domains, issues remain regarding early photochemical events, but common themes in conformational propagation have emerged across a diverse family of proteins. For BLUF proteins, photoinduced electron transfer reactions critical to light conversion are defined, but the subsequent rearrangement of hydrogen bonding networks key for signaling remains highly controversial. For CRYs, the relevant photocycles are actively debated, but mechanistic and functional studies are converging. Despite these challenges, our current understanding has enabled the engineering of flavoprotein photosensors for control of signaling processes within cells.

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Figure 1: Redox and protonation states of flavin (FAD or FMN).
Figure 2: LOV domain structure and reactivity.
Figure 3: Protein responses to LOV cysteinyl-adduct formation.
Figure 4: BLUF domain structure and reactivity.
Figure 5: CRY structure and reactivity.

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Acknowledgements

This work supported by NIH grants R01-GM079679 B.R.C., F32-GM099391 to K.S.C. and T32-GM008500 to C.C.M.

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Correspondence to Brian R Crane.

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Conrad, K., Manahan, C. & Crane, B. Photochemistry of flavoprotein light sensors. Nat Chem Biol 10, 801–809 (2014). https://doi.org/10.1038/nchembio.1633

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