5TE3

Photocyclic behavior of rhodopsin induced by an atypical isomerization mechanism.

(2017) Proc Natl Acad Sci U S A 114: E2608-E2615

• PubMed: 28289214 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1073/pnas.1617446114
• Primary Citation of Related Structures:  
  5TE3, 5TE5


• PubMed Abstract: 
  

  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 (G _t ) followed by chromophore release. Here we report that bovine Rh, regenerated instead with a six-carbon-ring retinal chromophore featuring a C ¹¹ =C ¹² 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 G _t activation. 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 G _t in response to light stimuli, making it an excellent candidate for optogenetic tools based on retinal analog-bound vertebrate Rhs. Overall, these comprehensive structure-function studies unveil a unique photocyclic mechanism of Rh activation by an 11- cis -to-11,13- dicis isomerization.

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Organizational Affiliation: 

Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106.