Comparative modeling of a GABAA alpha1 receptor using three crystal structures as templates

Journal of Molecular Graphics & Modelling
James R Trudell, Edward J Bertaccini

Abstract

We built a model of a GABAA alpha1 receptor (GABAAR) that combines the ligand binding (LBD) and the transmembrane domains (TMD). We used six steps: (1) a four-alpha helical bundle in the crystal structure of bovine cytochrome c oxidase (2OCC) was identified as a template for the TMD of a single subunit. (2) The five pore-forming alpha helices of a bacterial mechanosensitive channel (1MSL) served as a template for the pentameric ion channel. (3) Five copies of the tetrameric template from 2OCC were superimposed on 1MSL to produce a homopentamer containing 20 alpha helices arranged around a funnel-shaped central pore. (4) Five copies of the GABAAR sequence were threaded onto the alpha-helical segments of this template and inter-helical loops were generated to produce the TMD model. (5) A model of the LBD was built by threading the aligned sequence of GABAAR onto the crystal structure of the acetylcholine binding protein (1I9B). (6) The models of the LBD and the TMD were aligned along a common five-fold axis, moved together along that axis until in vdW contact, merged, and then optimized with restrained molecular dynamics. Our model corresponds closely with recently published coordinates of the acetylcholine receptor (1OED) but al...Continue Reading

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Citations

Sep 21, 2010·Quarterly Reviews of Biophysics·Andrew J ThompsonSarah C R Lummis
Jul 3, 2007·Journal of Chemical Information and Modeling·Edward J BertacciniErik Lindahl
Aug 18, 2010·ACS Chemical Neuroscience·Edward J BertacciniErik Lindahl
Jul 29, 2008·The Journal of Biological Chemistry·Daniel K CrawfordRonald L Alkana
Sep 10, 2010·The Journal of Pharmacology and Experimental Therapeutics·Mandy L McCrackenR Adron Harris
Aug 18, 2010·Neuropharmacology·John E Baenziger, Pierre-Jean Corringer
May 22, 2009·Journal of Neurochemistry·Isabelle M PaulsenSusan M J Dunn
Jun 15, 2007·Journal of Neurochemistry·Daniel K CrawfordRonald L Alkana
Aug 1, 2006·Journal of Molecular Graphics & Modelling·Valérie Campagna-Slater, Donald F Weaver
Nov 3, 2012·Journal of Chemical Information and Modeling·R S K VijayanNanda Ghoshal
Jun 15, 2007·Pharmacology & Therapeutics·Alastair M HosieTrevor G Smart
Jan 24, 2007·Anesthesia and Analgesia·Edward J BertacciniNicholas P Franks
Sep 22, 2005·The Journal of Biological Chemistry·Alexandra M PersonGregg B Wells
Jan 26, 2005·Journal of Chemical Information and Modeling·Edward J BertacciniJames R Trudell

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