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Mapping of GABR variants on the GABAA receptor.

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posted on 2016-09-13, 17:30 authored by Ciria C. Hernandez, Tara L. Klassen, Laurel G. Jackson, Katharine Gurba, Ningning Hu, Jeffrey L. Noebels, Robert L. Macdonald

(A), 3-D structural model of the GABAA receptor rendered with subunits arranged in a γ-β-α-β-α counter clockwise sequence as viewed from the synaptic cleft. The principal (+) and complementary (-) interfaces of each subunit are shown with the β subunits in blue, α subunits in red and γ subunit in grey. Eye arrows 1 and 2 at the β+/α- interfaces match the view of the models in panels B and C, respectively. (B, C), show side views of the full-length pentameric receptor structure at the β+/α- subunit interfaces mapping GEC (orange) and ESP (black) GABR variants. Eye arrow 0 indicates the view of the 3-D model in panel (A). (D) Multiple sequence alignment of GABR genes and the solved GluCl crystal structure (G5EBR3) as a reference for structural domains of the GABAA receptor. Locations of variants are highlighted in red for GEC and blue for ESP subunit variants. Secondary structures are indicated across GABR genes above the alignments, identical residues are highlighted in black and conserved residues in light grey. Each panel represents the succession in the sequence alignment where variants were found. Variants located in the signal peptide and M3/M4 cytoplasmic loop domains are not included.

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