Abstract
The fast kinetics characterizing the phototransduction cascade in virtually any species require that rhodopsin (Rh) form transient molecular complexes with a multitude of other proteins. Isolating such transient interactions in vitro and in vivo is a challenging task, although understanding their dynamics is essential to fully understand Rh function. Here, an established bottom-up systems biology approach is summarized, which links individual biomolecular processes to the whole-cell response, namely, the light-dependent suppression of the photoreceptor dark current. The known biochemical interactions occurring in the phototransduction cascade are integrated into a comprehensive computational model that can be numerically simulated, making it possible to: (a) virtually follow the time course of transient complexes formed by Rh with other molecules, including the cognate G protein transducin (Gt), rhodopsin kinase (RK), and arrestin (Arr), and (b) focus on specific receptor states, including multiple phosphorylations and activity of the chromophore-free receptor (opsin, Ops). Successful predictions of retinal disease-associated states, such as those related to vitamin A deficiency and Leber congenital amaurosis, have been obtained with the methodology presented herein.
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Acknowledgements
The methodology presented in this work is the result of a joint effort between several colleagues. I wish to acknowledge the fundamental contributions of Henning Schmidt, Brandon M. Invergo, Simona Mariani, Francesca Fanelli, and Karl-W. Koch. This work was supported by funds from the Italian Ministry of Research and Education, via departmental grants.
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Dell’Orco, D. (2015). Rhodopsin Transient Complexes Investigated by Systems Biology Approaches. In: Jastrzebska, B. (eds) Rhodopsin. Methods in Molecular Biology, vol 1271. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2330-4_17
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DOI: https://doi.org/10.1007/978-1-4939-2330-4_17
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