Directly light-regulated binding of RGS-LOV photoreceptors to anionic membrane phospholipids

Spencer T. Glantz, Erin E. Berlew, Zaynab Jaber, Benjamin S. Schuster, Kevin H. Gardner, Brian Y. Chow

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

We report natural light–oxygen–voltage (LOV) photoreceptors with a blue light-switched, high-affinity (KD ∼ 10−7 M), and direct electrostatic interaction with anionic phospholipids. Membrane localization of one such photoreceptor, BcLOV4 from Botrytis cinerea, 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.

Original languageEnglish (US)
Pages (from-to)E7720-E7727
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number33
DOIs
Publication statusPublished - Aug 14 2018

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Keywords

  • Light–oxygen–voltage domain
  • LOV
  • Optogenetics
  • Photobiology

ASJC Scopus subject areas

  • General

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