Electrostatic coupling between retinal isomerization and the ionization state of Glu-204: a general mechanism for proton release in bacteriorhodopsin

Biophys J. 1996 Sep;71(3):1165-71. doi: 10.1016/S0006-3495(96)79320-7.

Abstract

The pKa values of ionizable groups that lie between the active site region of bacteriorhodopsin (bR) and the extracellular surface of the protein are reported. Glu-204 is found to have an elevated pKa in the resting state of bR, suggesting that it corresponds to the proton-releasing group in bR. Its elevated pKa is predicted to be due in part to strong repulsive interactions with Glu-9. Following trans-cis isomerization of the retinal chromophore and the transfer of a proton to Asp-85, polar groups on the protein are able to interact more strongly with the ionized state of Glu-204, leading to a substantial reduction of its pKa. This suggests a general mechanism for proton release in which isomerization and subsequent charge separation initially produce a new electrostatic balance in the active site of bR. Here it is proposed that those events in turn drives a conformational change in the protein in which the ionized state of Glu-204 can be stabilized through interactions with groups that were previously inaccessible. Whether these groups should be identified with polar moieties in the protein, bound waters, or Arg-82 is an important mechanistic question whose elucidation will require further study.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacteriorhodopsins / chemistry*
  • Binding Sites
  • Biophysical Phenomena
  • Biophysics
  • Glutamic Acid / chemistry
  • Hydrogen-Ion Concentration
  • Ions
  • Isomerism
  • Models, Molecular
  • Molecular Structure
  • Protein Conformation
  • Protons
  • Retinaldehyde / chemistry
  • Static Electricity

Substances

  • Ions
  • Protons
  • Glutamic Acid
  • Bacteriorhodopsins
  • Retinaldehyde