Data from: A functionally conserved mechanism of modulation via a vestibule site in pentameric ligand-gated ion channels

Pentameric ligand-gated ion channels (pLGICs) belong to a class of ion
channels involved in fast synaptic signaling in the central and peripheral
nervous systems. Molecules acting as allosteric modulators target binding
sites that are remote from the neurotransmitter binding site, but
functionally affect coupling of ligand binding to channel opening. Here,
we investigated an allosteric binding site in the ion channel vestibule,
which has converged from a series of studies on prokaryote and eukaryote
channel homologs. We discovered single domain antibodies, called
nanobodies, which are functionally active as allosteric modulators, and
solved co-crystal structures of the prokaryote channel ELIC bound either
to a positive (PAM) or a negative (NAM) allosteric modulator. We
extrapolate the functional importance of the vestibule binding site to
eukaryote ion channels, suggesting a conserved mechanism of allosteric
modulation. This work identifies key elements of allosteric binding sites
and extends drug design possibilities in pLGICs using nanobodies.