7Y7Z
Cryo-EM structure of human GABA transporter GAT1 bound with tiagabine in NaCl solution in an inward-open state at 3.2 angstrom
Summary for 7Y7Z
| Entry DOI | 10.2210/pdb7y7z/pdb |
| Related | 7Y7V 7Y7W 7Y7X 7Y7Y |
| EMDB information | 33671 33672 33673 33674 33675 |
| Descriptor | Sodium- and chloride-dependent GABA transporter 1, Tiagabine, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | gaba transporter, gat1, nipecotic acid, tiagabine, neurotransmitter, slc6a1, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 71970.52 |
| Authors | |
| Primary citation | Zhu, A.,Huang, J.,Kong, F.,Tan, J.,Lei, J.,Yuan, Y.,Yan, C. Molecular basis for substrate recognition and transport of human GABA transporter GAT1. Nat.Struct.Mol.Biol., 30:1012-1022, 2023 Cited by PubMed Abstract: γ-Aminobutyric acid (GABA), an important inhibitory neurotransmitter in the central nervous system, is recycled through specific GABA transporters (GATs). GAT1, which is mainly expressed in the presynaptic terminals of axons, is a potential drug target of neurological disorders due to its essential role in GABA transport. Here we report four cryogenic electron microscopy structures of human GAT1, at resolutions of 2.2-3.2 Å. GAT1 in substrate-free form or in complex with the antiepileptic drug tiagabine exhibits an inward-open conformation. In the presence of GABA or nipecotic acid, inward-occluded structures are captured. The GABA-bound structure reveals an interaction network bridged by hydrogen bonds and ion coordination for GABA recognition. The substrate-free structure unwinds the last helical turn of transmembrane helix TM1a to release sodium ions and substrate. Complemented by structure-guided biochemical analyses, our studies reveal detailed mechanism of GABA recognition and transport, and elucidate mode of action of the inhibitors, nipecotic acid and tiagabine. PubMed: 37400655DOI: 10.1038/s41594-023-00983-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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