Conformational dynamics of a nicotinic receptor neurotransmitter site.

ABSTRACT: Agonists enhance receptor activity by providing net-favorable binding energy to active over resting conformations, with efficiency (η) linking binding energy to gating. Previously, we showed that in nicotinic receptors, η-values are grouped into five structural pairs, correlating efficacy and affinity within each class, uniting binding with allosteric activation (Indurthi and Auerbach, 2023). Here, we use molecular dynamics (MD) simulations to investigate the low-to-high affinity transition (L→H) at the Torpedo α-δ nicotinic acetylcholine receptor neurotransmitter site. Using four agonists spanning three η-classes, the simulations reveal the structural basis of the L→H transition where: the agonist pivots around its cationic center ('flip'), loop C undergoes staged downward displacement ('

SUBMITTER: Singh M 

PROVIDER: S-EPMC11655062 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature