The molecular determinants of neurosteroid binding in the GABA(A) receptor.

ABSTRACT: Neurosteroids positively modulate GABA-A receptor (GABA_AR) channel activity by binding to a transmembrane domain intersubunit site. Understanding the interactions in this site that determine neurosteroid binding and its effect is essential for the design of neurosteroid-based therapeutics. Using photo-affinity labeling and an ELIC-α1GABA_AR chimera, we investigated the impact of mutations (Q242L, Q242W and W246L) within the intersubunit site on neurosteroid binding. These mutations, which abolish the thermal stabilizing effect of allopregnanolone on the chimera, reduce neither photolabeling within the intersubunit site nor competitive prevention of labeling by allopregnanolone. Instead, these mutations change the orientation of neurosteroid photolabeling. Molecular doc

SUBMITTER: Sugasawa Y 

PROVIDER: S-EPMC6708749 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature