The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity

Nat Struct Mol Biol. 2010 Jan;17(1):44-50. doi: 10.1038/nsmb.1738. Epub 2009 Dec 20.

Abstract

In voltage-gated sodium, potassium and calcium channels, the functions of ion conduction and voltage sensing are performed by two distinct structural units: the pore domain and the voltage-sensing domain (VSD). In the hydrogen voltage-gated channel 1 (Hv1), the VSD, unusually, performs both functions. Hv1 was recently found to dimerize and to form channels made of two pores. However, the channels were also found to function when dimerization was prevented, raising a question about the functional role of dimerization. Here we show that the two subunits of the human Hv1 dimer influence one another during gating, with positive cooperativity shaping the response to voltage of the two pores. We also find that the two voltage sensors undergo conformational changes that precede pore opening and that these conformational changes are allosterically coupled between the two subunits. Our results point to an important role for dimerization in the modulation of Hv1 activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution / genetics
  • Animals
  • Fluorometry
  • Humans
  • Ion Channels / chemistry*
  • Ion Channels / metabolism*
  • Models, Molecular*
  • Patch-Clamp Techniques
  • Protein Conformation*
  • Protein Multimerization
  • Protein Structure, Tertiary*
  • Xenopus

Substances

  • HVCN1 protein, human
  • Ion Channels