Volatile anesthetic modulation of oligomerization equilibria in a hexameric model peptide.
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.
Ghirlanda
Giovanna
G
Department of Biophysics and Biochemistry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Hilcove
Simon A
SA
Pidikiti
Ravindernath
R
Johansson
Jonas S
JS
Lear
James D
JD
Degrado
William F
WF
Eckenhoff
Roderic G
RG
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D018685:Anesthetics, Inhalation / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D006221:Halothane / Q000737:chemistry / Q000378:metabolism*; D006859:Hydrogen / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D016415:Sequence Alignment; D014316:Tritium / Q000378:metabolism; D014461:Ultracentrifugation
D018685:Anesthetics, Inhalation; D010455:Peptides; D014316:Tritium; D006859:Hydrogen; D006221:Halothane