8v88 | pdb_00008v88

Alpha7-nicotinic acetylcholine receptor bound to epibatidine and GAT107

spinqualitylabelsall models 8v88, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8v88 is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.3Å Ligands: 9Z9, BMA, CA, EPJ, NAG, POV, YLI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease ACHA7_HUMAN 15q13.3 microdeletion syndrome. Function C562_ECOLX Electron-transport protein of unknown function.ACHA7_HUMAN After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin. Publication Abstract from PubMed The alpha7 nicotinic acetylcholine receptor is a pentameric ligand-gated ion channel that plays an important role in cholinergic signaling throughout the nervous system. Its unique physiological characteristics and implications in neurological disorders and inflammation make it a promising but challenging therapeutic target. Positive allosteric modulators overcome limitations of traditional alpha7 agonists, but their potentiation mechanisms remain unclear. Here, we present high-resolution structures of alpha7-modulator complexes, revealing partially overlapping binding sites but varying conformational states. Structure-guided functional and computational tests suggest that differences in modulator activity arise from the stable rotation of a channel gating residue out of the pore. We extend the study using a time-resolved cryoelectron microscopy (cryo-EM) approach to reveal asymmetric state transitions for this homomeric channel and also find that a modulator with allosteric agonist activity exploits a distinct channel-gating mechanism. These results define mechanisms of alpha7 allosteric modulation and activation with implications across the pentameric receptor superfamily. Structural mechanisms of alpha7 nicotinic receptor allosteric modulation and activation.,Burke SM, Avstrikova M, Noviello CM, Mukhtasimova N, Changeux JP, Thakur GA, Sine SM, Cecchini M, Hibbs RE Cell. 2024 Feb 29;187(5):1160-1176.e21. doi: 10.1016/j.cell.2024.01.032. Epub , 2024 Feb 20. PMID:38382524 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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