A state-dependent salt-bridge interaction exists across the β/α intersubunit interface of the GABAA receptor.

ABSTRACT: The GABA(A) receptor is a multisubunit protein that transduces the binding of a neurotransmitter at an intersubunit interface into the opening of a central ion channel. The structural components that mediate the steps involved in this action are poorly defined. A large amount of work has focused on clarifying the specific functions and interactions of residues believed to surround the GABA binding pocket. Here, we explored two charged residues (β(2)Asp163 and α(1)Arg120), which have been suggested by homology models to participate in a salt-bridge interaction. When mutated to alanine, both single mutants, as well as the double mutant, increase EC(50-GABA), decrease the GABA binding rate, and accelerate deactivation and GABA unbinding rates. Double-mutant cycle analysis demonstrates that th

SUBMITTER: Laha KT 

PROVIDER: S-EPMC3063723 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature