# Structures, Dynamics and Signaling Mechanisms of Modular Photoreceptors

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $378,328

## Abstract

Project Summary
The ability to sense and respond to complex environmental signals such as light, oxygen and nutrients is
critical for survival and adaptation of living organisms. Many signaling proteins adopt multi-domain modular
architecture to accomplish the perception of input signals and the generation of an output biological response
within the same protein molecule. One example of widespread modular systems is offered by bilin-based
photoreceptors in the phytochrome superfamily. Since light can readily penetrate the cell membrane, these
soluble multi-domain photoreceptors offer excellent model systems for studying the still elusive mechanism of
long-range signaling and allosteric regulation in modular signaling proteins such as chemoreceptors and
mechanoreceptors. Our long-term goal is to understand how modular photoreceptors perceive, integrate, and
transduce signals at the molecular level. To attack this goal, we adopt an integrated approach of biochemistry,
spectroscopy, crystallography and cryoEM single particle reconstruction, with a main thrust on dynamic
crystallography, which enables direct observation of structural responses at atomic resolution. In this proposal,
we use two dual-sensor photoreceptors to represent two major types of bilin-binding photoreceptors. Both are
sensory histidine kinases that feature different color perception and distinct signaling logic in response to light
or chemical signals. Previously, we have obtained abundant structural information on various isolated
domains by both static and dynamic crystallography. In this proposal, we will investigate the molecular
mechanisms of signal integration and allosteric activation in full-length proteins where the sensor and effector
domains are coupled. Specifically, we will capture structural changes in each sensory site by introducing
perturbations via ligand soaking and light illumination. We will examine how the structural signals are
initiated and how they propagate through the protein framework. We will jointly analyze the structures
determined in different signaling states to dissect subtle motions that may involve bending, torque,
winding/unwinding, or longitudinal sliding of helices. We will also perform mutagenesis and kinase assays to
identify the key structural elements responsible for signal coupling between the sensor domains, the helical
spine and the effector domain. We will determine the structures and dynamics of full-length photoreceptors by
complementary approaches of crystallography and electron microscopy to address whether the structural
asymmetry of the sensor and effector domains tethered in the same dimer scaffold plays an important role in
allosteric regulation of modular photoreceptors. Our results will not only apply to photoreceptors but will
inform the more general principles by which multi-domain signaling proteins such as the more widely studied
chemoreceptors detect and process complex environmental signals at the molecular level. Us...

## Key facts

- **NIH application ID:** 10219257
- **Project number:** 5R01EY024363-07
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Xiaojing Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,328
- **Award type:** 5
- **Project period:** 2014-05-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219257

## Citation

> US National Institutes of Health, RePORTER application 10219257, Structures, Dynamics and Signaling Mechanisms of Modular Photoreceptors (5R01EY024363-07). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10219257. Licensed CC0.

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