6W2Y
CryoEM Structure of GABAB1b Homodimer
Summary for 6W2Y
| Entry DOI | 10.2210/pdb6w2y/pdb |
| EMDB information | 21533 21534 |
| Descriptor | Gamma-aminobutyric acid type B receptor subunit 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | inhibitor, homodimer, gpcr, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 192425.99 |
| Authors | Papasergi-Scott, M.M.,Robertson, M.J.,Skiniotis, G. (deposition date: 2020-03-08, release date: 2020-07-01, Last modification date: 2024-10-30) |
| Primary citation | Papasergi-Scott, M.M.,Robertson, M.J.,Seven, A.B.,Panova, O.,Mathiesen, J.M.,Skiniotis, G. Structures of metabotropic GABABreceptor. Nature, 584:310-314, 2020 Cited by PubMed Abstract: Stimulation of the metabotropic GABA receptor by γ-aminobutyric acid (GABA) results in prolonged inhibition of neurotransmission, which is central to brain physiology. GABA belongs to family C of the G-protein-coupled receptors, which operate as dimers to transform synaptic neurotransmitter signals into a cellular response through the binding and activation of heterotrimeric G proteins. However, GABA is unique in its function as an obligate heterodimer in which agonist binding and G-protein activation take place on distinct subunits. Here we present cryo-electron microscopy structures of heterodimeric and homodimeric full-length GABA receptors. Complemented by cellular signalling assays and atomistic simulations, these structures reveal that extracellular loop 2 (ECL2) of GABA has an essential role in relaying structural transitions by ordering the linker that connects the extracellular ligand-binding domain to the transmembrane region. Furthermore, the ECL2 of each of the subunits of GABA caps and interacts with the hydrophilic head of a phospholipid that occupies the extracellular half of the transmembrane domain, thereby providing a potentially crucial link between ligand binding and the receptor core that engages G proteins. These results provide a starting framework through which to decipher the mechanistic modes of signal transduction mediated by GABA dimers, and have important implications for rational drug design that targets these receptors. PubMed: 32580208DOI: 10.1038/s41586-020-2469-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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