The GlyR Extracellular β8-β9 Loop - A Functional Determinant of Agonist Potency.

ABSTRACT: Ligand-binding of Cys-loop receptors results in rearrangements of extracellular loop structures which are further translated into the tilting of membrane spanning helices, and finally opening of the ion channels. The cryo-EM structure of the homopentameric α1 glycine receptor (GlyR) demonstrated an involvement of the extracellular β8-β9 loop in the transition from ligand-bound receptors to the open channel state. Recently, we identified a functional role of the β8-β9 loop in a novel startle disease mouse model shaky. The mutation of residue GlyRα1^Q177 to lysine present in shaky mice resulted in reduced glycine potency, reduced synaptic expression, and a disrupted hydrogen network at the structural level around position GlyRα1^Q177. Here, we investigated t

SUBMITTER: Janzen D 

PROVIDER: S-EPMC5640878 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature