Histidine residues regulate the transition of photoexcited rhodopsin to its active conformation, metarhodopsin II

The biologically active photoproduct of rhodopsin, metarhodopsin II (M II), exists in a pH-sensitive equilibrium with its precursor, metarhodopsin I (M I). Increasing acidity favors M 11, with the midpoint of the pH titration curve at pH 6.4. To test the long-standing proposal that histidine protona...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Neuron (Cambridge, Mass.) Mass.), 1992-03, Vol.8 (3), p.465-472
Hauptverfasser: Weitz, Charles J., Nathans, Jeremy
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:The biologically active photoproduct of rhodopsin, metarhodopsin II (M II), exists in a pH-sensitive equilibrium with its precursor, metarhodopsin I (M I). Increasing acidity favors M 11, with the midpoint of the pH titration curve at pH 6.4. To test the long-standing proposal that histidine protonation regulates this conformational transition, we characterized mutant rhodopsins in which each of the 6 histidines was replaced by phenylalanine or cysteine. Only mutants substituted at the 3 conserved histidines showed abnormal M I–M II equilibria. Those in which His-211 was replaced by phenylalanine or cysteine formed little or no M 11 at either extreme of pH, whereas mutants substituted at His-65 or at His-152 showed enhanced sensitivity to protons. The simplest interpretation of these results is that His-211 is the site where protonation strongly stabilizes the M I I conformation and that His-65 and His-152 are sites where protonation modestly destabilizes the M 11 conformation.
ISSN:0896-6273
1097-4199
DOI:10.1016/0896-6273(92)90274-H