# Structure-function studies of visual arrestin

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2020 · $597,997

## Abstract

PROJECT SUMMARY
We propose to elucidate the molecular mechanisms of arrestin-1 interactions with rhodopsin, which
significantly contribute to exquisitely regulated and precisely timed function of photoreceptor cells, using the
combination of novel cutting-edge biophysical methods and in vivo experiments. We will compare the shape of
the complex of arrestin-1 with rhodopsin using long-range distance measurements between selected points in
arrestin-1 and rhodopsin with pulse EPR technique DEER. We will explore the conformation of arrestin-bound
rhodopsin and compare it to the conformation of free light-activated rhodopsin and rhodopsin in complex with
transducing to determine whether particular conformation states of rhodopsin (a model GPCR) predispose it to
interact with G protein and arrestin. This is hypothesized in the field to be the basis of biased GPCR signaling.
We will determine the biological role of arrestin-1 self-association in photoreceptors in vivo, which is currently
unknown. Finally, we will test novel compensational approach to gene therapy of gain-of-function rhodopsin
mutations using engineered enhanced arrestin-1 mutants capable of shutting off rhodopsin signaling
independently of its phosphorylation. Proposed studies will significantly improve our understanding of
photoreceptor physiology and advance our progress towards gene therapy of gain-of-function rhodopsin
mutations. Due to high conservation of mechanics of GPCR regulation, mechanistic studies of arrestin-1
binding to rhodopsin will have broader implications, improving our understanding of the molecular basis of the
function of other arrestin subtypes. Proposed studies will shed new light on many aspects of cell signaling. Our
strategic goal is to gain sufficient understanding of protein-protein interactions that govern cell signaling to
construct mutants with desired functional characteristics for research and therapeutic purposes.

## Key facts

- **NIH application ID:** 9971298
- **Project number:** 2R01EY011500-23A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** VSEVOLOD V. GUREVICH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $597,997
- **Award type:** 2
- **Project period:** 1997-04-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971298

## Citation

> US National Institutes of Health, RePORTER application 9971298, Structure-function studies of visual arrestin (2R01EY011500-23A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9971298. Licensed CC0.

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