6DW0
Cryo-EM structure of the benzodiazepine-sensitive alpha1beta1gamma2S tri-heteromeric GABAA receptor in complex with GABA (Whole map)
Summary for 6DW0
| Entry DOI | 10.2210/pdb6dw0/pdb |
| Related | 6DW1 |
| EMDB information | 8922 8923 |
| Descriptor | Gamma-aminobutyric acid receptor subunit gamma-2, Gamma-aminobutyric acid receptor subunit alpha-1,Gamma-aminobutyric acid receptor subunit alpha-1, Gamma-aminobutyric acid receptor subunit beta-1,Gamma-aminobutyric acid receptor subunit beta-1, ... (8 entities in total) |
| Functional Keywords | neurotransmission, gaba receptors, gaba, cys loop receptors, ion channel, membrane protein |
| Biological source | Rattus norvegicus (Rat) More |
| Total number of polymer chains | 5 |
| Total formula weight | 242410.22 |
| Authors | Phulera, S.,Zhu, H.,Yu, J.,Yoshioka, C.,Gouaux, E. (deposition date: 2018-06-26, release date: 2018-08-08, Last modification date: 2024-11-20) |
| Primary citation | Phulera, S.,Zhu, H.,Yu, J.,Claxton, D.P.,Yoder, N.,Yoshioka, C.,Gouaux, E. Cryo-EM structure of the benzodiazepine-sensitive alpha 1 beta 1 gamma 2S tri-heteromeric GABAAreceptor in complex with GABA. Elife, 7:-, 2018 Cited by PubMed Abstract: 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. PubMed: 30044221DOI: 10.7554/eLife.39383 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.8 Å) |
Structure validation
Download full validation report
