A variety of studies are proposed to enhance our understanding of visual transduction, the process in which photon absorption in the retina is converted to an electrical impulse signaling light detection. In the past grant period, substantial progress was made in understanding the framework for the mechanism of visual pigment activation. Intermediates involved in activation were identified and their spectral characteristics, formation and decay kinetics, and how they were transformed from one intermediate to another, were determined. This places Dr. Kliger in an excellent position to now study the structural nature of these intermediates to gain a complete understanding of the activation mechanism of visual pigments. His potential for success has been enhanced tremendously with the recent report of the crystal structure of rhodopsin at 2.8 A resolution. This makes it possible to identify amino acid residues in the protein likely to be key in controlling the activation process. With his past progress in developing tools to make kinetic/spectroscopic measurements on minute quantities of pigments and his progress in elucidating the framework for activation, he is now in a unique position to gain a molecular level understanding of visual pigment activation. Given the structural similarities of rhodopsin and other G-protein coupled receptors, this information is likely to also be very important for gaining a molecular level understanding of how this important class of proteins function.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Molecular and Cellular Biophysics Study Section (BBCA)
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Mariani, Andrew P
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University of California Santa Cruz
Schools of Arts and Sciences
Santa Cruz
United States
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Szundi, Istvan; Funatogawa, Chie; Guo, Ying et al. (2017) Protein Sequence and Membrane Lipid Roles in the Activation Kinetics of Bovine and Human Rhodopsins. Biophys J 113:1934-1944
Szundi, Istvan; Funatogawa, Chie; Kliger, David S (2016) Complexity of Bovine Rhodopsin Activation Revealed at Low Temperature and Alkaline pH. Biochemistry 55:5095-105
Szundi, Istvan; Li, Hai; Chen, Eefei et al. (2015) Platymonas subcordiformis Channelrhodopsin-2 Function: I. THE PHOTOCHEMICAL REACTION CYCLE. J Biol Chem 290:16573-84
Szundi, Istvan; Bogomolni, Roberto; Kliger, David S (2015) Platymonas subcordiformis Channelrhodopsin-2 (PsChR2) Function: II. RELATIONSHIP OF THE PHOTOCHEMICAL REACTION CYCLE TO CHANNEL CURRENTS. J Biol Chem 290:16585-94
Mooney, Victoria L; Szundi, Istvan; Lewis, James W et al. (2012) Schiff base protonation changes in Siberian hamster ultraviolet cone pigment photointermediates. Biochemistry 51:2630-7
Kliger, David S; Chen, Eefei; Goldbeck, Robert A (2012) Probing kinetic mechanisms of protein function and folding with time-resolved natural and magnetic chiroptical spectroscopies. Int J Mol Sci 13:683-97
Tsukamoto, Hisao; Szundi, Istvan; Lewis, James W et al. (2011) Rhodopsin in nanodiscs has native membrane-like photointermediates. Biochemistry 50:5086-91
Chen, Eefei; Goldbeck, Robert A; Kliger, David S (2010) Nanosecond time-resolved polarization spectroscopies: tools for probing protein reaction mechanisms. Methods 52:3-11
Szundi, Istvan; Epps, Jacqueline; Lewis, James W et al. (2010) Temperature dependence of the lumirhodopsin I-lumirhodopsin II equilibrium. Biochemistry 49:5852-8
Thomas, Yiren Gu; Szundi, Istvan; Lewis, James W et al. (2009) Microsecond time-resolved circular dichroism of rhodopsin photointermediates. Biochemistry 48:12283-9

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