9W99
Structure of betaine-bound state of the human betaine/GABA transporter 1
Summary for 9W99
| Entry DOI | 10.2210/pdb9w99/pdb |
| EMDB information | 65767 |
| Descriptor | GFP,Maltose/maltodextrin-binding periplasmic protein,Sodium- and chloride-dependent betaine transporter, TRIMETHYL GLYCINE, SODIUM ION, ... (4 entities in total) |
| Functional Keywords | transport protein, membrane protein |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 1 |
| Total formula weight | 144619.29 |
| Authors | |
| Primary citation | Zhou, J.,Liu, J.,Jin, Y.,Wang, Q.,Yu, H.,Wu, J.X. Substrate recognition and allosteric inhibition of human betaine/GABA transporter 1. Nat Commun, 2026 Cited by PubMed Abstract: The betaine/GABA transporter 1 (BGT1, SLC6A12) regulates neurotransmitter clearance and osmotic balance by transporting GABA and betaine in a sodium- and chloride-dependent manner. BGT1 has become a promising target for epilepsy treatment due to the anticonvulsant effects observed with BGT1 inhibitors. Although BGT1 plays key roles in both renal and neuronal physiology, the molecular basis of its substrate recognition and inhibition remains unclear. Here, we report cryo-EM structures of human BGT1 in the apo form and in complex with GABA, betaine, the substrate-like inhibitor ATPCA, and the selective inhibitor BPDBA all without the use of fiducial markers. These structures capture BGT1 in both occluded and inward-facing conformations, delineating the conformational transitions associated with substrate release. BPDBA binds to an intracellular cavity adjacent to the intracellular gate. This binding mode locks TM1a to transit and inhibits substrate release. Together, our results uncover distinct mechanisms of substrate recognition and allosteric inhibition of hBGT1, offering structural insights for the development of hBGT1-selective modulators. PubMed: 42156742DOI: 10.1038/s41467-026-72924-5 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.04 Å) |
Structure validation
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