Allosteric coupling of sub-millisecond clamshell motions in ionotropic glutamate receptor ligand-binding domains.

ABSTRACT: Ionotropic glutamate receptors (iGluRs) mediate signal transmission in the brain and are important drug targets. Structural studies show snapshots of iGluRs, which provide a mechanistic understanding of gating, yet the rapid motions driving the receptor machinery are largely elusive. Here we detect kinetics of conformational change of isolated clamshell-shaped ligand-binding domains (LBDs) from the three major iGluR sub-types, which initiate gating upon binding of agonists. We design fluorescence probes to measure domain motions through nanosecond fluorescence correlation spectroscopy. We observe a broad kinetic spectrum of LBD dynamics that underlie activation of iGluRs. Microsecond clamshell motions slow upon dimerization and freeze upon binding of full and partial agonists. We uncover a

SUBMITTER: Rajab S 

PROVIDER: S-EPMC8429746 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature