Convergent evolution of tertiary structure in rhodopsin visual proteins from vertebrates and box jellyfish

Elliot Gerrard, Eshita Mutt, Takashi Nagata, Mitsumasa Koyanagi, Tilman Flock, Elena Lesca, Gebhard F.X. Schertler, Akihisa Terakita, Xavier Deupi, Robert J. Lucas

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9 Citations (Scopus)


Box jellyfish and vertebrates are separated by >500 million years of evolution yet have structurally analogous lens eyes that employ rhodopsin photopigments for vision. All opsins possess a negatively charged residue-the counterion-to maintain visible-light sensitivity and facilitate photoisomerization of their retinaldehyde chromophore. In vertebrate rhodopsins, the molecular evolution of the counterion position-from a highly conserved distal location in the second extracellular loop (E181) to a proximal location in the third transmembrane helix (E113)-is established as a key driver of higher fidelity photoreception. Here, we use computational biology and heterologous action spectroscopy to determine whether the appearance of the advanced visual apparatus in box jellyfish was also accompanied by changes in the opsin tertiary structure. We found that the counterion in an opsin from the lens eye of the box jellyfish Carybdea rastonii (JellyOp) has also moved to a unique proximal location within the transmembrane bundle-E94 in TM2. Furthermore, we reveal that this Schiff base/counterion system includes an additional positive charge-R186-that has coevolved with E94 to functionally separate E94 and E181 in the chromophore-binding pocket of JellyOp. By engineering this pocket-neutralizing R186 and E94, or swapping E94 with the vertebrate counterion E113-we can recreate versions of the invertebrate and vertebrate counterion systems, respectively, supporting a relatively similar overall architecture in this region of animal opsins. In summary, our data establish the third only counterion site in animal opsins and reveal convergent evolution of tertiary structure in opsins from distantly related species with advanced visual systems.

Original languageEnglish
Pages (from-to)6201-6206
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
Publication statusPublished - 12 Jun 2018
Externally publishedYes


  • Counterion
  • Evolution
  • G-protein-coupled receptors
  • Opsin
  • Vision

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