Rhodopsin as a Model for Other GPCRs

The years of research that have culminated in the various structures of rho-dopsin described here have not only benefited research into the mechanism and disorders of vision. In the absence of other GPCR structures, they have also provided an invaluable model and template for the entire GPCR family of receptors. Rhodopsin continues to be the model receptor, leading the way in our understanding of GPCR function at the molecule level. However, despite sharing many common features, seven transmembrane domains, conserved sequence motifs, and the ability to couple to G proteins, rhodopsin is less than 25% homologous to most other Family A GPCRs and has no homol-ogy with the other GPCR families, such as the secretin (Family B) and metabo-tropic (Family C) receptors. Nevertheless, pioneering work in the development of methods for obtaining crystal structures of rhodopsin, including methods for purification, selection of detergents, and conditions for crystallization, as well as the construction of stabilized mutants, has paved the way for the breakthroughs in obtaining the structures of other GPCRs, which are now described. The availability of other GPCR structures will enable us to determine just how good a model rhodopsin has been.

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