Mutations at the M2 and M3 Transmembrane Helices of the GABA_ARs α₁ and β₂ Subunits Affect Primarily Late Gating Transitions Including Opening/Closing and Desensitization.

ABSTRACT: GABA type A receptors (GABA_ARs) belong to the pentameric ligand-gated ion channel (pLGIC) family and play a crucial role in mediating inhibition in the adult mammalian brain. Recently, a major progress in determining the static structure of GABA_ARs was achieved, although precise molecular scenarios underlying conformational transitions remain unclear. The ligand binding sites (LBSs) are located at the extracellular domain (ECD), very distant from the receptor gate at the channel pore. GABA_AR gating is complex, comprising three major categories of transitions: openings/closings, preactivation, and desensitization. Interestingly, mutations at, e.g., the ligand binding site affect not only binding but often also more than one gating category, suggesting that s

SUBMITTER: Terejko K 

PROVIDER: S-EPMC8291490 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature