Structural bases for stoichiometry-selective calcium potentiation of a neuronal nicotinic receptor.

ABSTRACT:

Background and purpose

α4β2 nicotinic acetylcholine (nACh) receptors assemble in two stoichiometric forms, one of which is potentiated by calcium. The sites of calcium binding that underpin potentiation are not known.

Experimental approach

To identify calcium binding sites, we applied cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) simulations to each stoichiometric form of the α4β2 nACh receptor in the presence of calcium ions. To test whether the identified calcium sites are linked to potentiation, we generated mutants of anionic residues at the sites, expressed wild type and mutant receptors in clonal mammalian fibroblasts, and recorded ACh-elicited single-channel currents with or without calcium.

Key results

Both cryo-EM and MD simulations show calc

SUBMITTER: Mazzaferro S 

PROVIDER: S-EPMC12048133 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature