Three-dimensional model for meta-II rhodopsin, an activated G-protein-coupled receptor

A novel approach that iteratively combined the results of energy calculations and experimental data was used to generate a three-dimensional (3D) model of the photoactivated state (R*) of bovine rhodopsin (Rh). The approach started with simplified energy calculations in an effort to find a set of sterically and energetically reasonable options for transmembrane (TM) helix arrangements with all-trans-retinal. Various 3D models of TM helix packing found by computations were then compared to limited site-directed spin-label experimental data regarding the transition of the TM helices of Rh in the inactive state (R) to those in the R* state to identify the most plausible model of the TM helical bundle. At the next step, all non-TM structural elements, such as the non-TM helix 8, the N- and C-terminal fragments, and the loops connecting TM helices, were reconstructed, and after the entire R* structure had been relaxed, all other currently available additional experimental data, both mutational and spectroscopic, on the structure of the meta-II state of rhodopsin were used to validate the resulting 3D model.