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TitleStructure and gating mechanism of the α7 nicotinic acetylcholine receptor.
Journal, issue, pagesCell, Vol. 184, Issue 8, Page 2121-2134.e13, Year 2021
Publish dateApr 15, 2021
AuthorsColleen M Noviello / Anant Gharpure / Nuriya Mukhtasimova / Rico Cabuco / Leah Baxter / Dominika Borek / Steven M Sine / Ryan E Hibbs /
PubMed AbstractThe 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 ...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.
External linksCell / PubMed:33735609 / PubMed Central
MethodsEM (single particle)
Resolution2.7 - 3.6 Å
Structure data

22979

7koo

EMDB-22979, PDB-7koo:
Alpha-7 nicotinic acetylcholine receptor bound to alpha-bungarotoxin in a resting state
Method: EM (single particle) / Resolution: 3.0 Å

22980

7koq

EMDB-22980, PDB-7koq:
Alpha-7 nicotinic acetylcholine receptor bound to epibatidine in a desensitized state
Method: EM (single particle) / Resolution: 3.6 Å

22983

7kox

EMDB-22983, PDB-7kox:
Alpha-7 nicotinic acetylcholine receptor bound to epibatidine and PNU-120596 in the activated state
Method: EM (single particle) / Resolution: 2.7 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-CA:
Unknown entry

ChemComp-EPJ:
EPIBATIDINE / alkaloid*YM

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • bungarus multicinctus (many-banded krait)
  • escherichia coli (E. coli)
KeywordsMEMBRANE PROTEIN / Cys-loop receptor

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