The C-terminal coiled-coil of the bacterial voltage-gated sodium channel NaChBac is not essential for tetramer formation, but stabilizes subunit-to-subunit interactions

Prog Biophys Mol Biol. 2010 Sep;103(1):111-21. doi: 10.1016/j.pbiomolbio.2010.05.002. Epub 2010 May 26.

Abstract

The NaChBac is a prokaryotic homologue of the voltage-gated sodium channel found in the genome of the alkalophilic bacterium Bacillus halodurans C-125. Like a repeating cassette of mammalian sodium channel, the NaChBac possesses hydrophobic domains corresponding to six putative transmembrane segments and a pore loop, and exerts channel function by forming a tetramer although detailed mechanisms of subunit assembly remain unclear. We generated truncated mutants from NaChBac, and investigated their ability to form tetramers in relation to their channel functions. A mutant that deletes almost all of the C-terminal coiled-coil structure lost its voltage-dependent ion permeability, although it was properly translocated to the cell surface. The mutant protein was purified as a tetramer using a reduced concentration of detergent, but the association between the subunits was shown to be much weaker than the wild type. The chemical cross-linking, blue native PAGE, sedimentation velocity experiments, size exclusion chromatography, immunoprecipitation, and electron microscopy all supported its tetrameric assembly. We further purified the C-terminal cytoplasmic domain alone and confirmed its self-oligomerization. These data suggest that the C-terminal coiled-coil structure stabilizes subunit-to-subunit interactions of NaChBac, but is not critical for their tetramer formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus / metabolism*
  • Biotin / chemistry
  • Biotin / metabolism
  • Cross-Linking Reagents / chemistry
  • Cytoplasm / chemistry
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • Electrophoresis
  • Electrophysiology
  • Hydrophobic and Hydrophilic Interactions
  • Immunoprecipitation
  • Ion Channel Gating / genetics
  • Ion Channel Gating / physiology*
  • Mutation
  • Protein Multimerization
  • Protein Stability
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Sodium Channels / chemistry*
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Ultracentrifugation

Substances

  • Cross-Linking Reagents
  • Protein Subunits
  • Sodium Channels
  • Biotin