On the Bioactive Conformation of the Rhodopsin Chromophore: Absolute Sense of Twist around the 6-s-cis Bond

• Published in: Chemistry : a European journal Vol. 7; no. 19; pp. 4198 - 4204
• Main Authors: Fujimoto, Yukari, Ishihara, Jun, Maki, Shojiro, Fujioka, Naoko, Wang, Tao, Furuta, Takumi, Fishkin, Nathan, Borhan, Babak, Berova, Nina, Nakanishi, Koji
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag GmbH 01.10.2001; WILEY‐VCH Verlag GmbH; Wiley
• Subjects: Animals; Cattle; Chemistry; Chemistry, Multidisciplinary; chirality; Circular Dichroism; conformation analysis; Models, Molecular; Physical Sciences; Protein Conformation; Protein Structure, Secondary; receptors; retinal; Retinaldehyde - analogs & derivatives; rhodopsin; Rhodopsin - chemistry; Rod Opsins - chemistry; Science & Technology; Spectrophotometry, Ultraviolet; Stereoisomerism; conformation analysis; retinal; chirality; receptors; MECHANISM; SCHIFF-BASE COUNTERION; circular dichroism; MODEL; IDENTIFICATION; rhodopsin; BOVINE RHODOPSIN; RETINAL CHROMOPHORE; VISUAL EXCITATION; THEORETICAL-ANALYSIS
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/1521-3765(20011001)7:19<4198::AID-CHEM4198>3.0.CO;2-X

Incubation of opsin with synthetic 6‐s‐locked retinoids 2 a and 2 b only led to pigment formation from the alpha‐locked 2 a, the CD spectrum of which was similar to that of native rhodopsin (Rh). This establishes that the 6‐s‐bond of the chromophore in rhodopsin is cis, and that its helicity is negative. Earlier cross‐linking studies showed that the 11‐cis to all‐trans photoisomerization occurring in the batho‐Rh to lumi‐Rh conversion induces a flip over of the side carrying the ring moiety. The GTP‐binding assay of pigment Rh‐(2 a), incorporating retinal analogue 2 a, has shown that its activity is 80 % that of the native pigment. That is, the overall conformation around the 6‐s bond is retained in the steps leading to G‐protein activation. Incubation of opsin with synthetic 6‐s‐locked enantiomeric retinoids only led to pigment formation from the α‐locked isomer; the CD spectrum of which was similar to that of native rhodopsin (Rh). This establishes that the 6‐s‐bond of the chromophore in rhodopsin is cis, as shown, and that its helicity is negative.