Structure/function relationships in the arrestin protein. The function of arrestin to inactivate rhodopsin in phototransduction was well established by several laboratories in the 1980’s. However, the mechanism by which arrestin selectively binds and quenches only light-activated, phosphorylated rhodopsin was unclear and has significant implications for the majority of the G-protein-coupled receptor family. Work in our lab and with a team of collaborators mapped the surface of arrestin that interacted with rhodopsin. This work was the first to demonstrate that multiple smaller conformational changes in arrestin, rather than large domain movements, were responsible for driving the selectivity of arrestin for phosphorylated, photoactivated rhodopsin, a finding that has been born out for the broader class of G-protein-coupled receptors.
- Sommer ME, Farrens DL, McDowell JH, Weber LA, Smith WC (2007) Dynamics of arrestin-rhodopsin interactions: loop movement is involved in arrestin activation and receptor binding. J. Biol. Chem. 282: 25560-25568.
- Smith WC, Dinculescu A, Peterson JJ, McDowell JH (2004) The surface of visual arrestin that binds to rhodopsin. Molec. Vision 10: 392-398.
- Dinculescu A, McDowell JH, Amici SA, Dugger DR, Richards N, Hargrave PA, Smith WC (2002) An insertional mutagenesis and immunochemical analysis of visual arrestin interaction with rhodopsin. J. Biol. Chem. 277: 11703-11708.
- Smith WC, McDowell JH, Dugger DR, Miller R, Arendt A, Popp MP, Hargrave PA (1999) Identification of regions of arrestin that bind to rhodopsin. Biochem. 38: 2752-2761.