Volatile anesthetic modulation of oligomerization equilibria in a hexameric model peptide

Giovanna Ghirlanda, Simon A. Hilcove, Ravindernath Pidikiti, Jonas S. Johansson, James D. Lear, William F. DeGrado, Roderic G. Eckenhoff

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)140-144
Number of pages5
JournalFEBS Letters
Volume578
Issue number1-2
DOIs
StatePublished - Dec 3 2004

Keywords

  • Analytical ultracentrifugation
  • Anesthesia
  • Halothane
  • Hydrogen exchange
  • Protein cavities

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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    Ghirlanda, G., Hilcove, S. A., Pidikiti, R., Johansson, J. S., Lear, J. D., DeGrado, W. F., & Eckenhoff, R. G. (2004). Volatile anesthetic modulation of oligomerization equilibria in a hexameric model peptide. FEBS Letters, 578(1-2), 140-144. https://doi.org/10.1016/j.febslet.2004.10.087