Visual arrestin-1: how did we learn what we know today about this protein?

Proteins are studied using a wide variety of methods, each with its inherent limitations. Here we analyze the contributions of different methods to our understanding of one of the most extensively studied proteins, arrestin-1, which plays a key role in the regulation of light-evoked signaling of photopigments in the photoreceptor cells in the retina. The data obtained by biochemical and biophysical methods in vitro are consistent with the results of in vivo studies in genetically modified mice and the symptoms seen in human patients. The structures of free arrestin-1 and its complex with rhodopsin provided very detailed information and stimulated structure-function studies. However, while the results of follow-up experiments confirmed some predictions from the crystal structures, they were inconsistent with others. In particular, the arrestin-1 tetramer in solution and in the photoreceptors of living mice was shown to be dramatically different from that revealed by the crystal structures. The prevalent complex (es) of wild type arrestin-1 with rhodopsin also appear to differ from the one in the solved structure of the two interacting mutant proteins. The lessons learned with arrestin-1 likely also apply to other proteins.