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• W2080218576 endingPage "1277" @default.
• W2080218576 startingPage "1266" @default.
• W2080218576 abstract "The GABAC receptor and closely related GABAA receptor are members of the pentameric ligand-gated ion channels (pLGICs) superfamily and mediate inhibitory fast synaptic transmission in the nervous system. Each pLGIC subunit comprises an N-terminal extracellular agonist-binding domain followed by a channel domain and a variable intracellular domain. Available structural information shows that the core of the agonist-binding domain is a β sandwich of ten β-strands, which form the agonist-binding pocket at the subunit interface. This β-sandwich is preceded by an N-terminal α-helix in eukaryotic structures but not in prokaryotic structures. The N-terminal α-helix has been shown to be functionally essential in α7 nicotinic acetylcholine receptors. Sequence analysis of GABAC and GABAA receptors predicts an α-helix in a similar position but preceded by 8 to 46 additional residues, of unknown function, which we term the N-terminal extension. To test the functional role of both the N-terminal extension and the putative N-terminal α-helix in the ρ1 GABAC receptor, we created a series of deletions from the N-terminus. The N-terminal extension was not functionally essential, but its removal did reduce both cell surface expression and cooperativity of agonist-gated channel function. Further deletion of the putative N-terminal α-helix abolished receptor function by preventing cell-surface expression. Our results further demonstrate the essential role of the N-terminal α-helix in the assembly and trafficking of eukaryotic pLGICs. They also provide evidence that the N-terminal extension, although not essential, contributes to receptor assembly, trafficking and conformational changes associated with ligand gating." @default.
• W2080218576 created "2016-06-24" @default.
• W2080218576 creator A5023919017 @default.
• W2080218576 creator A5076611678 @default.
• W2080218576 creator A5078695405 @default.
• W2080218576 date "2014-10-27" @default.
• W2080218576 modified "2023-10-02" @default.
• W2080218576 title "Role of the ρ1 GABA_C Receptor N-Terminus in Assembly, Trafficking and Function" @default.
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• W2080218576 doi "https://doi.org/10.1021/cn500220t" @default.
• W2080218576 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25347026" @default.
• W2080218576 hasPublicationYear "2014" @default.
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