7koo

Publication Abstract from PubMed

The alpha7 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(2+), and desensitizes faster than any other Cys-loop receptor. The alpha7 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 alpha7 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 alpha7 structures provide a foundation for mapping the gating cycle and reveal divergence in gating mechanisms in the Cys-loop receptor superfamily.

Structure and gating mechanism of the alpha7 nicotinic acetylcholine receptor.,Noviello CM, Gharpure A, Mukhtasimova N, Cabuco R, Baxter L, Borek D, Sine SM, Hibbs RE Cell. 2021 Mar 11. pii: S0092-8674(21)00238-5. doi: 10.1016/j.cell.2021.02.049. PMID:33735609^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.