Direct gating of ATP-activated ion channels (P2X2 receptors) by lipophilic attachment at the outer end of the second transmembrane domain

Simon W. Rothwell, Phillip J. Stansfeld, Laricia Bragg, Alexej Verkhratsky, R. Alan North

Research output: Contribution to journalArticlepeer-review

Abstract

Background: ATP-gated (P2X) receptors form pores with second transmembrane helices from each of three subunits. Results: Addition of an unbranched lipophilic group at I328C in P2X2 receptors opened the channel as effectively as ATP. Conclusion: Destabilizing the Ile328/Val48 interaction allows the Ile328 side chain to move laterally and open the pore. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)618-626
Number of pages8
JournalJournal of Biological Chemistry
Volume289
Issue number2
DOIs
Publication statusPublished - 10 Jan 2014

Keywords

  • Adenosine Triphosphate/chemistry/metabolism/*pharmacology
  • Amino Acid Substitution
  • Binding Sites/genetics
  • HEK293 Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Ion Channel Gating/genetics/*physiology
  • Ion Channels/chemistry/genetics/*physiology
  • Lipid Bilayers/chemistry/metabolism
  • Membrane Potentials/drug effects/genetics/physiology
  • Mesylates/chemistry/metabolism/pharmacology
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Mutation
  • Patch-Clamp Techniques
  • Protein Structure, Tertiary
  • Receptors, Purinergic P2X2/chemistry/genetics/*physiology

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