8V89
Alpha7-nicotinic acetylcholine receptor time resolved resting state
Summary for 8V89
| Entry DOI | 10.2210/pdb8v89/pdb |
| Related | 8UT1 8UTB 8UZJ 8V80 8V82 8V86 8V88 8V8A 8V8C 8V8D |
| EMDB information | 43031 |
| Descriptor | Neuronal acetylcholine receptor subunit alpha-7,Soluble cytochrome b562, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | ion channel, membrane protein, nicotinic receptor |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 349110.65 |
| Authors | Burke, S.M.,Noviello, C.M.,Hibbs, R.E. (deposition date: 2023-12-05, release date: 2024-02-21, Last modification date: 2024-10-30) |
| Primary citation | Burke, S.M.,Avstrikova, M.,Noviello, C.M.,Mukhtasimova, N.,Changeux, J.P.,Thakur, G.A.,Sine, S.M.,Cecchini, M.,Hibbs, R.E. Structural mechanisms of alpha 7 nicotinic receptor allosteric modulation and activation. Cell, 187:1160-1176.e21, 2024 Cited by PubMed Abstract: The α7 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 α7 agonists, but their potentiation mechanisms remain unclear. Here, we present high-resolution structures of α7-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 α7 allosteric modulation and activation with implications across the pentameric receptor superfamily. PubMed: 38382524DOI: 10.1016/j.cell.2024.01.032 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.53 Å) |
Structure validation
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