Volatile anesthetic modulation of oligomerization equilibria in a hexameric model peptide

FEBS Lett. 2004 Dec 3;578(1-2):140-4. doi: 10.1016/j.febslet.2004.10.087.


To determine if occupancy of interfacial pockets in oligomeric proteins by volatile anesthetic molecules can allosterically regulate oligomerization equilibria, variants of a three-helix bundle peptide able to form higher oligomers were studied with analytical ultracentrifugation, hydrogen exchange and modeling. Halothane shifted the oligomerization equilibria towards the oligomer only in a mutation predicted to create sufficient volume in the hexameric pocket. Other mutations at this residue, predicted to create a too small or too polar pocket, were unaffected by halothane. Inhaled anesthetic modulation of oligomerization interactions is a novel and potentially generalizable biophysical basis for some anesthetic actions.

MeSH terms

  • Allosteric Regulation
  • Amino Acid Sequence
  • Anesthetics, Inhalation / chemistry
  • Anesthetics, Inhalation / metabolism*
  • Binding Sites
  • Halothane / chemistry
  • Halothane / metabolism*
  • Hydrogen / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / metabolism
  • Protein Structure, Quaternary*
  • Sequence Alignment
  • Tritium / metabolism
  • Ultracentrifugation


  • Anesthetics, Inhalation
  • Peptides
  • Tritium
  • Hydrogen
  • Halothane