title: Functional and topological diversity of LOV domain photoreceptors.
abstract: Light-oxygen-voltage sensitive (LOV) flavoproteins are ubiquitous photoreceptors that mediate responses to environmental cues. Photosensory inputs are transduced into signaling outputs via structural rearrangements in sensor domains that consequently modulate the activity of an effector domain or multidomain clusters. Establishing the diversity in effector function and sensor-effector topology will inform what signaling mechanisms govern light-responsive behaviors across multiple kingdoms of life and how these signals are transduced. Here, we report the bioinformatics identification of over 6,700 candidate LOV domains (including over 4,000 previously unidentified sequences from plants and protists), and insights from their annotations for ontological function and structural arrangements. Motif analysis identified the sensors from ∼42 million ORFs, with strong statistical separation from other flavoproteins and non-LOV members of the structurally related Per-aryl hydrocarbon receptor nuclear translocator (ARNT)-Sim family. Conserved-domain analysis determined putative light-regulated function and multidomain topologies. We found that for certain effectors, sensor-effector linker length is discretized based on both phylogeny and the preservation of α-helical heptad repeats within an extended coiled-coil linker structure. This finding suggests that preserving sensor-effector orientation is a key determinant of linker length, in addition to ancestry, in LOV signaling structure-function. We found a surprisingly high prevalence of effectors with functions previously thought to be rare among LOV proteins, such as regulators of G protein signaling, and discovered several previously unidentified effectors, such as lipases. This work highlights the value of applying genomic and transcriptomic technologies to diverse organisms to capture the structural and functional variation in photosensory proteins that are vastly important in adaptation, photobiology, and optogenetics.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Spencer T
authors.initials: ST
authors.lastname: Glantz
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada T6G 2E9;
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Carpenter
authors.affiliation: Institute of Botany, Cologne Biocenter, University of Cologne, 50674 Cologne, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Melkonian
authors.affiliation: Structural Biology Initiative, CUNY Advanced Science Research Center, City College of New York, New York, NY 10031; Department of Chemistry and Biochemistry, City College of New York, New York, NY 10031; Biochemistry, Chemistry and Biology Programs, Graduate Center, The City University of New York, New York, NY 10031;
authors.forename: Kevin H
authors.identifier: http://orcid.org/0000-0002-8671-2556
authors.initials: KH
authors.lastname: Gardner
authors.affiliation: The Media Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; McGovern Institute for Brain Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Edward S
authors.initials: ES
authors.lastname: Boyden
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada T6G 2E9; Department of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2E1; BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Gane Ka-Shu
authors.initials: GK
authors.lastname: Wong
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104; bchow@seas.upenn.edu.
authors.forename: Brian Y
authors.initials: BY
authors.lastname: Chow
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D005420:Flavoproteins / Q000737:chemistry* / Q000378:metabolism*; D008027:Light; D016366:Open Reading Frames; D017956:Photoreceptor Cells, Invertebrate / Q000737:chemistry / Q000378:metabolism; D020283:Photoreceptors, Microbial / Q000737:chemistry / Q000378:metabolism; D055519:Photoreceptors, Plant / Q000737:chemistry / Q000378:metabolism; D011381:Programming Languages; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D005420:Flavoproteins; D020283:Photoreceptors, Microbial; D055519:Photoreceptors, Plant
keywords: LOV; flavoproteins; optogenetics; photoreceptors