# Mechanism of activation and modulation in human GABA(B) receptor

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $18,575

## Abstract

Summary
The inhibitory neurotransmitter GABA produces slow and prolonged inhibition in the brain through
activation of metabotropic GABAB receptors. Defects in GABAB signaling have been implicated in
various neurological and mood disorders including spasticity, epilepsy, addiction and anxiety. GABAB
receptor is a member of the class C G protein-coupled receptor (GPCR) family, which typically
functions as a dimer and possesses large extracellular domains. Fundamental questions remain
concerning the molecular mechanisms underlying activation and modulation of these class C receptors.
The GABAB receptor is a heterodimer of GABAB1 and GABAB2 subunits and is modulated by the
potassium channel tetramerization domain-containing (KCTD) protein auxiliary subunits. We are
developing structural models for full-length GABAB receptor, its auxiliary subunits and their complexes
with G-protein. Based on our structural analysis, we will determine the molecular association between
GABAB receptor and KCTD, describe the conformations of full-length GABAB receptor in multiple
functional states, and characterize the allosteric interaction between the GABAB receptor and G
proteins. Together, these studies will advance our understanding of the molecular basis of GABA action
in the brain, leading to the development of novel therapeutics for treating neurological diseases.

## Key facts

- **NIH application ID:** 10388693
- **Project number:** 3R01GM125801-03S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** QING R FAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $18,575
- **Award type:** 3
- **Project period:** 2018-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388693

## Citation

> US National Institutes of Health, RePORTER application 10388693, Mechanism of activation and modulation in human GABA(B) receptor (3R01GM125801-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10388693. Licensed CC0.

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