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Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Photoactivation of G Protein-coupled Receptor Rhodopsin

Transmembrane signal transduction by G protein-coupled receptors is an essential biological process. Our work addresses the molecular mechanism of G protein-coupled receptor activation using the visual photoreceptor rhodopsin as a model system. We investigated the structure of the chromophore in the primary photoproduct of rhodopsin using an interdisciplinary approach. We obtained resonance Raman vibrational spectra of several recombinant site-directed mutants of rhodopsin and was able to determine the structural basis for the unusual decoupled hydrogen-out-of-plane wagging frequencies of the chromophore in bathorhodopsin by simulating spectral data using density functional theory calculations (1). These results explain how photon energy is stored in early rhodopsin photoproducts and converted to mechanical energy, which drives subsequent protein conformational changes. We showed that transmembrane helix movement, which is required for receptor activation, is driven by an ionic switching mechanism (2). The switch involves protein carboxylic acid side chains and an internal hydrogen-bond network that links an extracelluar loop and specific transmembrane helices of the receptor to movement of the protonated Schiff base of the chromophore (3). This counterion switch may be a general feature of all visual pigments and has implications for understanding the activation mechanisms of other seven-helical G protein-coupled receptors.

References and Footnotes
  1. Yan, E. C. Y., Gamin, Z., Kazmi, M. A., Chang, B. S. W., Sakmar, T. P., Mathies, R. A. Biochemistry 43, 10867, 2004.
  2. Yan, E. C. Y., Kazmi, M. A., Gamin, Z., Hou, J. M., Pan, D., Chang, B. S. W., Sakmar, T. P., Mathies, R. A Proc Natl Acad Sci USA 100, 9262, 2003.
  3. Yan, E. C. Y., Lewis, J. W., Szundi, I., Epps, J., Bhagat, A., Kliger, D.S. Accepted to J Phy Chem B, 2006.

Elsa C. Y. Yan

YaleUniversity
Dept of Chemistry
New Haven CT 06520

Phone: 203-432-3915
Fax: 203-432-6244
Email: yane@rockefeller.edu