# Photosensory LOV proteins: Study and application of signaling mechanisms

> **NIH NIH R01** · ADVANCED SCIENCE RESEARCH CENTER · 2020 · $333,435

## Abstract

ABSTRACT
Among the environmental factors that influence biology, light controls an incredibly rich set of processes
including circadian rhythms, movement and development. Central to this regulation are diverse families of
photoreceptors that harness the photochemically-triggered configurational changes of light-sensitive cofactors,
the chemical properties of which confer sensitivity to specific portions of the UV and visible spectrum. These
structural alterations are amplified as allosteric changes in the surrounding protein, initiating signal transduction
pathways that control biological responses. Understanding how these initial sensing and signaling events are
triggered has given insight into fundamental aspects of biology and enabled the development of novel
optogenetic tools that are enabling discoveries in diverse fields of biomedicine. Here we focus on examining
both signaling mechanism and applicability to tool development for proteins containing LOV (Light-Oxygen-
Voltage) photosensory domains. These domains are found in thousands of proteins to date, controlling the
activity of over 20 enzymatic and non-enzymatic effector domains in natural systems and many others in
engineered proteins. To do so, LOV domains undergo the specific photochemical formation of protein/flavin
adducts upon illumination with blue light, using this as a trigger to allosterically drive protein conformational
changes around the flavin. This configurational change is allosterically transmitted to the surrounding protein,
providing a light-based “switch” of protein activity that remains engaged until illumination ceases. Fundamental
questions regarding these signaling processes remain unanswered, limiting our understanding of natural and
engineered LOV proteins. We propose to answer these limitations by pursuing three aims: 1). Determine the
lit state structures of two classes of activated LOV proteins to give insight into signaling and guiding future
engineering efforts; 2). Establish the correlation of in vitro photochemical and DNA-binding parameters on
cellular function of a LOV-controlled transcription factor tools; 3). Examine the generality of LOV signaling
models by determining the structural role of photosensing in a novel class of RGS-LOV signaling proteins. To
achieve these ends, we will take advantage of an broad foundation of preliminary structural and functional data
that will be extended with a mix of biophysical and biochemical studies. Outcomes from this research will
include information about fundamental regulatory processes employed by these proteins, giving insights that
will be broadly applicable for signal transduction studies.

## Key facts

- **NIH application ID:** 9928063
- **Project number:** 5R01GM106239-09
- **Recipient organization:** ADVANCED SCIENCE RESEARCH CENTER
- **Principal Investigator:** Kevin H Gardner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $333,435
- **Award type:** 5
- **Project period:** 2013-09-30 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928063

## Citation

> US National Institutes of Health, RePORTER application 9928063, Photosensory LOV proteins: Study and application of signaling mechanisms (5R01GM106239-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9928063. Licensed CC0.

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