Functional role of internal water molecules in rhodopsin revealed by x-ray crystallography

Tetsuji Okada, Yoshinori Fujiyoshi, Maria Silow, Javier Navarro, Ehud M. Landau, Yoshinori Shichida

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Abstract

Activation of G protein-coupled receptors (GPCRs) is triggered and regulated by structural rearrangement of the transmembrane heptahelical bundle containing a number of highly conserved residues. In rhodopsin, a prototypical GPCR, the helical bundle accommodates an intrinsic inverse-agonist 11-cis-retinal, which undergoes photo-isomerization to the all-trans form upon light absorption. Such a trigger by the chromophore corresponds to binding of a diffusible ligand to other GPCRs. Here we have explored the functional role of water molecules in the transmembrane region of bovine rhodopsin by using x-ray diffraction to 2.6 Å. The structural model suggests that water molecules, which were observed in the vicinity of highly conserved residues and in the retinal pocket, regulate the activity of rhodopsin-like GPCRs and spectral tuning in visual pigments, respectively. To confirm the physiological relevance of the structural findings, we conducted single-crystal microspectrophotometry on rhodopsin packed in our three-dimensional crystals and show that its spectroscopic properties are similar to those previously found by using bovine rhodopsin in suspension or membrane environment.

Original languageEnglish (US)
Pages (from-to)5982-5987
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number9
DOIs
StatePublished - Apr 30 2002

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ASJC Scopus subject areas

  • Genetics
  • General

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