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Key receptor involved in neuronal signalling visualized

Proteins called GABAA receptors have a pivotal role in neuronal inhibition, and are targets of several drugs. Structures of the most abundant GABAA receptor in humans are now reported, and will aid future drug discovery.
  1. Erwin Sigel

    1. Erwin Sigel is at the Institute of Biochemistry and Molecular Medicine, Medical Faculty, University of Bern, 3010 Bern, Switzerland.

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The daytime biological activity of humans is based on a delicate equilibrium between excitatory and inhibitory signalling in the brain. The neurotransmitter molecule that mediates the main inhibitory signal is γ-aminobutyric acid (GABA), which binds to and activates ion channels, including a family known as GABAA receptors1 found in the cell membranes of neurons. The activity of these receptors is modulated by many drugs2, including sedatives, anxiolytics and sleeping pills. GABAA receptors can be assembled from several types of subunit, and the most abundant GABAA receptors in the adult human brain consist of two α1 subunits, two β2 subunits and one γ2 subunit. In a paper in Nature, Zhu et al.3 present two structures of this receptor isoform in complex with GABA and a drug molecule known as flumazenil, providing much-needed insight that will aid future drug-discovery efforts.

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Nature 559, 37-38 (2018)

doi: https://doi.org/10.1038/d41586-018-05538-7

See Editorial: Brain-protein structure could point way to safer prescription drugs

References

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