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-Structure paper
タイトル | Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABA receptor in complex with GABA. |
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ジャーナル・号・ページ | Elife, Vol. 7, Year 2018 |
掲載日 | 2018年7月25日 |
![]() | Swastik Phulera / Hongtao Zhu / Jie Yu / Derek P Claxton / Nate Yoder / Craig Yoshioka / Eric Gouaux / ![]() |
PubMed 要旨 | Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Native GABA ...Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Native GABA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABA receptors implicated in multiple neurological diseases. Despite the profound importance of heteromeric GABA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination. Here we present the structure of a tri-heteromeric α1β1γ2S GABA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding. Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating. Our work provides a pathway to structural studies of heteromeric GABA receptors and a framework for rational design of novel therapeutic agents. |
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手法 | EM (単粒子) |
解像度 | 3.1 - 3.8 Å |
構造データ | EMDB-8922: Cryo-EM structure of the benzodiazepine-sensitive alpha1-beta1-gamma2 heterotrimeric GABAA receptor in complex with GABA |
化合物 | ![]() ChemComp-ABU: |
由来 |
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![]() | MEMBRANE PROTEIN / Neurotransmission / GABA Receptors / GABA / Cys Loop Receptors / Ion Channel |