# Structural biology of G protein-coupled receptors

> **NIH NIH R35** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $412,500

## Abstract

Abstract
G protein-coupled receptors (GPCRs) constitute the largest membrane protein superfamily in the human
genome, with over 800 unique sequences. GPCR-mediated signaling pathways play a key role in all
physiological systems as well as many pathophysiological conditions, and therefore represent important drug
targets. GPCRs have a seven-transmembrane-helix (7TM) topology and contain multiple binding sites for
orthosteric ligands and allosteric modulators. Upon recognition of their native ligands receptors transmit signals
across the cell membrane to intracellular partner proteins, such as G proteins or β-arrestins. Developing a
detailed understanding of functional mechanisms of GPCRs and facilitating design of novel drugs with high
selectivity and potency require access to high-resolution three-dimensional structures, determination of which,
however, remains a challenging task. We propose here a comprehensive research program which combines
technology development with integrated structure-function studies focused on the GPCR superfamily. The
proposed research directions are designed to accelerate high-resolution structure determination of membrane
proteins, improve our understanding of the GPCR superfamily and answer specific questions on ligand specificity
and selectivity, as well as molecular mechanisms of action using several specific receptors as targets. Our
approach integrates structural information on new receptors and complexes with data obtained from biophysical,
biochemical and functional experiments through computer-based analysis and modeling. The long-term goal of
our laboratory is to develop a deeper understanding of the molecular mechanisms of action of GPCRs using the
tools of structural biology, and to use the achieved insights to accelerate the design and development of novel
and efficacious therapeutics.

## Key facts

- **NIH application ID:** 9925243
- **Project number:** 5R35GM127086-03
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Vadim Cherezov
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925243

## Citation

> US National Institutes of Health, RePORTER application 9925243, Structural biology of G protein-coupled receptors (5R35GM127086-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9925243. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*