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Intrasubunit and Intersubunit Steroid Binding Sites Independently and Additively Mediate α1β2γ2L GABA_A Receptor Potentiation by the Endogenous Neurosteroid Allopregnanolone.

ABSTRACT: Prior work employing functional analysis, photolabeling, and X-ray crystallography have identified three distinct binding sites for potentiating steroids in the heteromeric GABA_A receptor. The sites are located in the membrane-spanning domains of the receptor at the β-α subunit interface (site I) and within the α (site II) and β subunits (site III). Here, we have investigated the effects of mutations to these sites on potentiation of the rat α1β2γ2L GABA_A receptor by the endogenous neurosteroid allopregnanolone (3α5αP). The mutations were introduced alone or in combination to probe the additivity of effects. We show that the effects of amino acid substitutions in sites I and II are energetically additive,

SUBMITTER: Germann AL

PROVIDER: S-EPMC8256884 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Dataset Information

Intrasubunit and Intersubunit Steroid Binding Sites Independently and Additively Mediate α1β2γ2L GABA_A Receptor Potentiation by the Endogenous Neurosteroid Allopregnanolone.

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Dataset Information

Intrasubunit and Intersubunit Steroid Binding Sites Independently and Additively Mediate α1β2γ2L GABAA Receptor Potentiation by the Endogenous Neurosteroid Allopregnanolone.

OmicsDI is part of the ELIXIR infrastructure

Tweets

Intrasubunit and Intersubunit Steroid Binding Sites Independently and Additively Mediate α1β2γ2L GABA_A Receptor Potentiation by the Endogenous Neurosteroid Allopregnanolone.