7KOO

Alpha-7 nicotinic acetylcholine receptor bound to alpha-bungarotoxin in a resting state

Summary for 7KOO

• Entry DOI: 10.2210/pdb7koo/pdb
• EMDB information: 22979
• Descriptor: Neuronal acetylcholine receptor subunit alpha-7,Soluble cytochrome b562 fusion, Alpha-bungarotoxin isoform V31, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: cys-loop receptor, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 364943.17

Authors

Noviello, C.M.,Hibbs, R.E.,Gharpure, A.,Mukhtasimova, N.,Cabuco, R.,Baxter, L.,Borek, D.,Sine, S. (deposition date: 2020-11-09, release date: 2021-03-17, Last modification date: 2021-05-12)

Primary citation

Noviello, C.M.,Gharpure, A.,Mukhtasimova, N.,Cabuco, R.,Baxter, L.,Borek, D.,Sine, S.M.,Hibbs, R.E.
Structure and gating mechanism of the alpha 7 nicotinic acetylcholine receptor.
Cell, 184:2121-, 2021

PubMed Abstract: The α7 nicotinic acetylcholine receptor plays critical roles in the central nervous system and in the cholinergic inflammatory pathway. This ligand-gated ion channel assembles as a homopentamer, is exceptionally permeable to Ca, and desensitizes faster than any other Cys-loop receptor. The α7 receptor has served as a prototype for the Cys-loop superfamily yet has proven refractory to structural analysis. We present cryo-EM structures of the human α7 nicotinic receptor in a lipidic environment in resting, activated, and desensitized states, illuminating the principal steps in the gating cycle. The structures also reveal elements that contribute to its function, including a C-terminal latch that is permissive for channel opening, and an anionic ring in the extracellular vestibule that contributes to its high conductance and calcium permeability. Comparisons among the α7 structures provide a foundation for mapping the gating cycle and reveal divergence in gating mechanisms in the Cys-loop receptor superfamily.

PubMed: 33735609
DOI: 10.1016/j.cell.2021.02.049

Experimental method

ELECTRON MICROSCOPY (3 Å)