We report natural light-oxygen-voltage (LOV) photoreceptors with a blue light-switched， high-affinity ( ∼ 10 M)， and direct electrostatic interaction with anionic phospholipids. Membrane localization of one such photoreceptor， BcLOV4 from ， is directly coupled to its flavin photocycle， and is mediated by a polybasic amphipathic helix in the linker region between the LOV sensor and its C-terminal domain of unknown function (DUF)， as revealed through a combination of bioinformatics， computational protein modeling， structure-function studies， and optogenetic assays in yeast and mammalian cell line expression systems. In model systems， BcLOV4 rapidly translocates from the cytosol to plasma mem... More
We report natural light-oxygen-voltage (LOV) photoreceptors with a blue light-switched， high-affinity ( ∼ 10 M)， and direct electrostatic interaction with anionic phospholipids. Membrane localization of one such photoreceptor， BcLOV4 from ， is directly coupled to its flavin photocycle， and is mediated by a polybasic amphipathic helix in the linker region between the LOV sensor and its C-terminal domain of unknown function (DUF)， as revealed through a combination of bioinformatics， computational protein modeling， structure-function studies， and optogenetic assays in yeast and mammalian cell line expression systems. In model systems， BcLOV4 rapidly translocates from the cytosol to plasma membrane (∼1 second). The reversible electrostatic interaction is nonselective among anionic phospholipids， exhibiting binding strengths dependent on the total anionic content of the membrane without preference for a specific headgroup. The in vitro and cellular responses were also observed with a BcLOV4 homolog and thus are likely to be general across the dikarya LOV class， whose members are associated with regulator of G-protein signaling (RGS) domains. Natural photoreceptors are not previously known to directly associate with membrane phospholipids in a light-dependent manner， and thus this work establishes both a photosensory signal transmission mode and a single-component optogenetic tool with rapid membrane localization kinetics that approaches the diffusion limit.
