A variety of studies are proposed which will enhance our understanding of the nature of visual transduction. Particular attention will be paid to the changes which take place in visual pigments upon absorption of light which initiate the visual transduction process. This will be done on several levels. Photochemical processes in polyenes will be investigated because the initial step in transduction involves a photoisomerization of the retinal chromophore of visual pigments. Understanding what influences the isomerization process in polyenes will help us understand how this process is mediated in the protein. The photointermediates of both native and artificially modified visual pigments will also be studied. What intermediates are formed, how they transform into one another, and what properties they have will be studied by time-resolved absorption spectroscopy. Most of this work will be carried out on bovine rhodopsin and related pigments but the work will also be extended to the study of human rhodopsin. Recently, studies have linked some retinal diseases to a wide variety of specific mutations in the rhodopsin gene. This suggests that the functioning of rhodopsin is directly related to human visual disorders. It is thus important to understand the how rhodopsin functions. Studies of the bovine system are important as sufficient material is available to obtain a detailed understanding of the protein function. Extensions to the study of human rhodopsin are also important if we are to relate human visual disorders to rhodopsin function.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY000983-22
Application #
2158040
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1977-04-01
Project End
1996-09-29
Budget Start
1994-09-30
Budget End
1995-09-29
Support Year
22
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California Santa Cruz
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Santa Cruz
State
CA
Country
United States
Zip Code
95064
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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