Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a.

Academic Article

Abstract

  • Acid-sensing ion channels are ligand-gated cation channels, gated by extracellular H(+). H(+) is the simplest ligand possible, and whereas for larger ligands that gate ion channels complex binding sites in the three-dimensional structure of the proteins have to be assumed, H(+) could in principle gate a channel by titration of a single amino acid. Experimental evidence suggests a more complex situation, however. For example, it has been shown that extracellular Ca(2+) ions compete with H(+); probably Ca(2+) ions bound to the extracellular loop of ASICs stabilize the closed state of the channel and have to be displaced before the channel can open. In such a scheme, amino acids contributing to Ca(2+) binding would also be candidates contributing to H(+) gating. In this study we systematically screened more than 40 conserved, charged amino acids in the extracellular region of ASIC1a for a possible contribution to H(+) gating. We identified four amino acids where substitution strongly affects H(+) gating: Glu(63), His(72)/His(73), and Asp(78). These amino acids are highly conserved among H(+)-sensitive ASICs and are candidates for the "H(+) sensor" of ASICs.
  • Authors

  • Paukert, Martin
  • Chen, Xuanmao
  • Polleichtner, Georg
  • Schindelin, Hermann
  • GrĂ¼nder, Stefan
  • Status

    Publication Date

  • January 4, 2008
  • Published In

    Keywords

  • Acid Sensing Ion Channels
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Amino Acids
  • Animals
  • Aspartic Acid
  • Binding Sites
  • Calcium
  • Female
  • Glutamic Acid
  • Histidine
  • Hydrogen-Ion Concentration
  • Ion Channel Gating
  • Membrane Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • Oocytes
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Rats
  • Sequence Homology, Amino Acid
  • Sodium Channels
  • Structure-Activity Relationship
  • Xenopus laevis
  • Digital Object Identifier (doi)

    Pubmed Id

  • 17981796
  • Start Page

  • 572
  • End Page

  • 581
  • Volume

  • 283
  • Issue

  • 1