The molecular basis for the high photosensitivity of rhodopsin

doi:10.1073/pnas.2536769100

The molecular basis for the high photosensitivity of rhodopsin

Department of Chemistry, University of Hawaii, Honolulu, HI 96822

Communicated by George S. Hammond, Allied Signal Corporation, Portland, OR, October 20, 2003 (received for review August 30, 2003)

Abstract

Based on structural information derived from the F NMR data of labeled rhodopsins, rhodopsin crystal structure, and excited-state properties of model polyenes, we propose a molecular mechanism that accounts specifically for the causes of the well-known enhanced photoreactivity of rhodopsin (increased rates and quantum yield of isomerization). It involves the key features of close proximity of C-187 to H-12 and chromophore bond lengthening upon light absorption. The resultant “sudden punch” to H-12 triggers dual processes of decay of the Franck–Condon-excited rhodopsin, a productive directed photoisomerization and a nonproductive decay returning to the ground state as two separate molecular pathways [based on real-time fluorescence results of Chosrowjan, H., Mataga, N., Shibata, Y., Tachibanaki, S., Kandori, H., Shichida, Y., Okada, T. & Kouyama, T. (1998) J. Am. Chem. Soc. 120, 9706–9707]. The two processes are controlled by the local protein structure: an empty space provided by the intradiscal loop connecting transmembrane helices 4 and 5 and a protein wall composed of amino acid units in transmembrane 3. Suggestions, involving retinal analogs and rhodopsin mutants, to improve the unusually high photosensitivity of rhodopsin are proposed.

Footnotes

↵ † To whom correspondence should be addressed. E-mail: rliu{at}gold.chem.hawaii.edu.
Abbreviations: BP, bicycle pedal; FC, Franck-Condon; FOS, fluorine opsin shift; HT, hula twist; PSB, protonated Schiff base; TM, transmembrane.
↵ ‡ Dr. T. Mirzadegan (Hoffmann–La Roche) first brought to our attention the unique location of Cys-187 (personal communication).
↵ § In other words, light absorption causes H-12 to “bang” itself into the protein wall (Cys-187) at lightning speed, a Hawaiian punch (?).
↵ ¶ Deuterium isotope effects (at H-11 and H-12) on the early excited-state processes of rhodopsin are in the literature (65). But the effect is relatively small and appears to be rather complex, varying at different time delays.