9BVH
Homomeric alpha3 glycine receptor in the presence of 0.1 mM glycine in an apo state.
Summary for 9BVH
| Entry DOI | 10.2210/pdb9bvh/pdb |
| EMDB information | 44933 |
| Descriptor | Glycine receptor subunit alpha-3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate, ... (6 entities in total) |
| Functional Keywords | glycine, ion channel, ligand-gated, pentameric, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 5 |
| Total formula weight | 310470.73 |
| Authors | Kindig, K.,Gibbs, E.,Chakrapani, S. (deposition date: 2024-05-20, release date: 2024-11-13, Last modification date: 2025-05-28) |
| Primary citation | Kindig, K.,Gibbs, E.,Seiferth, D.,Biggin, P.C.,Chakrapani, S. Mechanisms underlying modulation of human GlyR alpha 3 by Zn 2+ and pH. Sci Adv, 10:eadr5920-eadr5920, 2024 Cited by PubMed Abstract: Glycine receptors (GlyRs) regulate motor control and pain processing in the central nervous system through inhibitory synaptic signaling. The subtype GlyRα3 expressed in nociceptive sensory neurons of the spinal dorsal horn is a key regulator of physiological pain perception. Disruption of spinal glycinergic inhibition is associated with chronic inflammatory pain states, making GlyRα3 an attractive target for pain treatment. GlyRα3 activity is modulated by numerous endogenous and exogenous ligands that consequently affect pain sensitization. To understand the mechanism of two such endogenous modulators, Zn and protons, we have used cryo-electron microscopy to determine structures of full-length human GlyRα3 in various functional states. Whereas acidic pH reduces peak glycine response, Zn displays biphasic modulation in a concentration-dependent manner. Our findings reveal the effector sites and also capture intermediate conformations in the gating cycle. Combined with molecular dynamics simulations and electrophysiology, this work provides important insights into GlyRα3 activation and regulation. PubMed: 39693447DOI: 10.1126/sciadv.adr5920 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.58 Å) |
Structure validation
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