STRUCTURAL STUDIES OF RHODOPSIN

Cornell University, Ithaca NY

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We are carrying out a series of structural characterizations of biologically important forms of rhodopsin, the light-sensing membrane protein found in retina, and related proteins. Rhodopsin was the first G protein-coupled receptor for which crystallographic structural information became available. It remains a prototypical GPCR. This makes it of considerable interest because GPCRs are the major target of many commercially important drugs. We are crystallizing rhodopsin and rhodopsin/transducin complexes to obtain the structure of an activated GPCR and its complex with its cognate G protein. By observing the structural changes associated with signal transduction, we will identify regions in the three-dimensional molecular structure that are crucial for the biological activity of this and other GPCRs. Those regions will become the focus of other biochemical studies and drug-development activities.