Conformational flexibility of the ligand-binding domain dimer in kainate receptor gating and desensitization.

ABSTRACT: AMPA- and kainate (KA)-selective ionotropic glutamate receptors (iGluRs) respond to agonist by opening (gating), then closing (desensitizing) in quick succession. Gating has been linked to agonist-induced changes within the ligand-binding domain (LBD), and desensitization to rearrangement of a dimer formed by neighboring LBDs. To explore the role of dimer conformation in both gating and desensitization, we compared the conformational effects of two kainate receptor mutants. The first, GluK2-D776K, blocks desensitization of macroscopic current responses ("macroscopic desensitization"). The second, GluK2-M770K, accelerates macroscopic desensitization and eliminates the effects of external ions on channel kinetics. Using structures determined by x-ray crystallography, we found that in both mu

SUBMITTER: Nayeem N 

PROVIDER: S-EPMC6623771 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature