Modulation of the <i>Erwinia</i> ligand-gated ion channel (ELIC) and the 5-HT₃ receptor via a common vestibule site.

ABSTRACT: Pentameric ligand-gated ion channels (pLGICs) or Cys-loop receptors are involved in fast synaptic signaling in the nervous system. Allosteric modulators bind to sites that are remote from the neurotransmitter binding site, but modify coupling of ligand binding to channel opening. In this study, we developed nanobodies (single domain antibodies), which are functionally active as allosteric modulators, and solved co-crystal structures of the prokaryote (Erwinia) channel ELIC bound either to a positive or a negative allosteric modulator. The allosteric nanobody binding sites partially overlap with those of small molecule modulators, including a vestibule binding site that is not accessible in some pLGICs. Using mutagenesis, we extrapolate the functional importance of the vestibule bind

SUBMITTER: Brams M 

PROVIDER: S-EPMC7015668 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature