title: Rhodopsin transient complexes investigated by systems biology approaches.
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.
authors.affiliation: Department of Life Sciences and Reproduction, Section of Biological Chemistry, University of Verona, Strada le Grazie 8, 37134, Verona, Italy, daniele.dellorco@univr.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Dell'Orco
mesh_terms: D019393:Arrestin / Q000737:chemistry* / Q000378:metabolism; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*; D015293:Transducin / Q000737:chemistry / Q000378:metabolism
chemical_list: D019393:Arrestin; D012243:Rhodopsin; D051606:G-Protein-Coupled Receptor Kinase 1; D015293:Transducin