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Title: Photocyclic behavior of rhodopsin induced by an atypical isomerization mechanism

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [1];  [2];  [1];  [3];  [1];  [4];  [1]; ORCiD logo [3];  [1]; ORCiD logo [5];  [4];  [1]; ORCiD logo [1]
  1. Case Western Reserve Univ., Cleveland, OH (United States)
  2. Cornell Univ., Ithaca, NY (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
  3. Univ. of Warsaw (Poland)
  4. Novartis Inst. for BioMedical Research, Cambridge, MA (United States)
  5. Case Western Reserve Univ., Cleveland, OH (United States); Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH (United States)

Vertebrate rhodopsin (Rh) contains 11-cis-retinal as a chromophore to convert light energy into visual signals. On absorption of light, 11-cis-retinal is isomerized to all-trans-retinal, constituting a one-way reaction that activates transducin (Gt) followed by chromophore release. Here we report that bovine Rh, regenerated instead with a six-carbon-ring retinal chromophore featuring a C11=C12 double bond locked in its cis conformation (Rh6mr), employs an atypical isomerization mechanism by converting 11-cis to an 11,13-dicis configuration for prolonged Gt activation. We report time-dependent UV-vis spectroscopy, HPLC, and molecular mechanics analyses revealed an atypical thermal reisomerization of the 11,13-dicis to the 11-cis configuration on a slow timescale, which enables Rh6mr to function in a photocyclic manner similar to that of microbial Rhs. With this photocyclic behavior, Rh6mr repeatedly recruits and activates Gt in response to light stimuli, making it an excellent candidate for optogenetic tools based on retinal analog-bound vertebrate Rhs. Overall, we report these comprehensive structure–function studies unveil a unique photocyclic mechanism of Rh activation by an 11-cis–to–11,13-dicis isomerization.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
National Institutes of Health (NIH); US Department of Veterans Affairs; National Science Foundation (NSF); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division
Grant/Contract Number:
AC02-06CH11357; EY021126; EY027283; EY025214; CA157735; IK2BX002683; MCB-084480; P41 GM103403; S10 RR029205
OSTI ID:
1368263
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, Issue 13; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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