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Structural biology of synaptic and extrasynaptic GABAA receptors


EMSL Project ID
51259

Abstract

GABAA receptors are pentameric ligand-gated ion channels and mediate the majority of fast inhibitory signaling in the brain. Here we propose to characterize the structural pharmacology of receptors that are found at synapses as well as receptor subtypes found outside of synapses to understand principles of drug selectivity and receptor architecture. We aim to examine structural complexes with benzodiazepines, anesthetics and a physiological ethanol antagonist. The results will reveal the architectures of difference conformational states of the receptors in principles of ligand recognition underpinning the particularly rich pharmacology of this ligand-gated ion channel family.

Project Details

Start Date
2020-01-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Ryan Hibbs
Institution
University of Texas Southwestern Medical Center

Team Members

Weronika Chojnacka
Institution
University of Texas Southwestern Medical Center

Dagimhiwat Legesse
Institution
University of Texas Southwestern Medical Center

Jeong Joo Kim
Institution
University of Texas Southwestern Medical Center

Colleen Noviello
Institution
University of Texas Southwestern Medical Center

Harry Scott
Institution
Oregon Health & Science University

Related Publications

Shared structural mechanisms of general anaesthetics and benzodiazepines. Kim JJ, Gharpure A, Teng J, Zhuang Y, Howard RJ, Zhu S, Noviello CM, Walsh RM Jr, Lindahl E, Hibbs RE. Nature. 2020 Sep 2. doi: 10.1038/s41586-020-2654-5. Online ahead of print. PMID: 32879488