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 (G t), 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.
CITATION STYLE
Dell’Orco, D. (2015). Rhodopsin transient complexes investigated by systems biology approaches. Methods in Molecular Biology, 1271, 251–263. https://doi.org/10.1007/978-1-4939-2330-4_17
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