We use the proteins rhodopsin and transducin as models for structure-function studies of the molecular mechanism of the visual transduction pathway. These proteins, which are found in the retina, are members of a superfamily of related GPCRs and G proteins (guanine nucleotide-binding regulatory proteins). Our approach is to clone and characterize genes for relevant signaling pathways and then reconstitute expressed proteins in defined in vitro systems. Biochemical and biophysical methods are then used to examine the functional significance of specific protein domains or amino acid residues.

Rhodopsin, the receptor for dim-light detection in the rod cell of the retina, is an excellent prototype for biophysical studies of the GPCR superfamily. Light-activated rhodopsin catalyzes guanine nucleotide exchange by the G protein transducin, which ultimately leads to a change in membrane cation conductance and a neural signal.

We are studying the ground state structure of rhodopsin, the interactions between specific amino acid residues and its vitamin A chromophore that control spectral properties and photochemistry, the mechanism by which a photochemical signal is transmitted from the core of the receptor to its cellular surface, and the specific domains on the cellular surface that bind and activate transducin.

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