2MAW
NMR structures of the alpha7 nAChR transmembrane domain.
Summary for 2MAW
| Entry DOI | 10.2210/pdb2maw/pdb |
| NMR Information | BMRB: 19379 |
| Descriptor | Neuronal acetylcholine receptor subunit alpha-7 (1 entity in total) |
| Functional Keywords | transmembrane domain, membrane protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein: P36544 |
| Total number of polymer chains | 1 |
| Total formula weight | 14582.00 |
| Authors | Bondarenko, V.,Mowrey, D.,Xu, Y.,Tang, P. (deposition date: 2013-07-19, release date: 2013-11-13, Last modification date: 2024-05-15) |
| Primary citation | Mowrey, D.D.,Liu, Q.,Bondarenko, V.,Chen, Q.,Seyoum, E.,Xu, Y.,Wu, J.,Tang, P. Insights into distinct modulation of alpha 7 and alpha 7 beta 2 nicotinic acetylcholine receptors by the volatile anesthetic isoflurane. J.Biol.Chem., 288:35793-35800, 2013 Cited by PubMed Abstract: Nicotinic acetylcholine receptors (nAChRs) are targets of general anesthetics, but functional sensitivity to anesthetic inhibition varies dramatically among different subtypes of nAChRs. Potential causes underlying different functional responses to anesthetics remain elusive. Here we show that in contrast to the α7 nAChR, the α7β2 nAChR is highly susceptible to inhibition by the volatile anesthetic isoflurane in electrophysiology measurements. Isoflurane-binding sites in β2 and α7 were found at the extracellular and intracellular end of their respective transmembrane domains using NMR. Functional relevance of the identified β2 site was validated via point mutations and subsequent functional measurements. Consistent with their functional responses to isoflurane, β2 but not α7 showed pronounced dynamics changes, particularly for the channel gate residue Leu-249(9'). These results suggest that anesthetic binding alone is not sufficient to generate functional impact; only those sites that can modulate channel dynamics upon anesthetic binding will produce functional effects. PubMed: 24194515DOI: 10.1074/jbc.M113.508333 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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