Bioinformatics Discovery And Functional Characterization Of Lipid-Binding Lov Photoreceptors

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Doctor of Philosophy (PhD)
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Photosensory signaling
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The light–oxygen–voltage sensitive (LOV) domain subset of the PAS superfamily is a ubiquitous photoreceptor class that enables organisms across multiple kingdoms to sense blue light. LOV photoreceptors are modular flavin-binding proteins that consist of discrete sensor and effector domains. Blue-light drives a LOV sensor to trigger a conformational change in photoreceptor structure that ultimately regulates the biochemical function of one or more of its fused effectors. The nature by which LOV photoreceptors vary in their sensor-effector domain combinations allows for light-gated regulation by a single-photoreceptor class of diverse physiological processes across species in varied ecological settings that underlie circadian rhythms, virulence, phototropism, and stress responses. Here, we report the bioinformatics identification of over 6,700 candidate LOV domains and their annotation for sensor-effector topology and inferred ontological function. In addition to nearly tripling the number of reported LOV sequences, we identified several classes of LOV proteins with predicted sensor-effector pairings that were previously unknown or considered rare and thus have yet to be functionally characterized, including photoreceptors with LOV sensors and Regulator of G-protein signaling (RGS) and PAS homology effectors (“RGS-LOV-PAS”) in dikarya fungi and brown algae. We report the experimental characterization of two bioinformatics-identified fungal RGS-LOV-PAS photoreceptors, BcRGS5 from B cinerea and CeRGS from C. europaea, that rapidly localize from cytoplasm to the plasma membrane upon blue-light illumination in a heterologous mammalian cell expression system. Dynamic membrane localization by BcRGS5 is mediated by a light-switchable high affinity electrostatic interaction with anionic phospholipids. The seconds-timescale membrane-recruitment, likely driven by a conserved lipid-binding amphipathic helix, may serve to potentiate RGS effector activity on membrane-bound binding partners in the native fungal organism. As neither LOV photoreceptors nor RGS proteins nor PAS sensory proteins are known to traffic by light-gated and direct association with phospholipids, this work establishes a novel photosensory signaling mechanism for multiple protein classes and highlights the value of applying genomic technologies to diverse organisms to capture photosensory protein diversity that is vastly important in adaptation, photobiology, and optogenetics.

Brian Y. Chow
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