The Cytoplasmic Rhodopsin-Protein Interface: Potential for Drug Discovery

Title: The Cytoplasmic Rhodopsin-Protein Interface: Potential for Drug Discovery

Volume: 13 Issue: 1

Author(s): Naveena Yanamala, Eric Gardner, Alec Riciutti and Judith Klein-Seetharaman

Affiliation:

Keywords: G protein coupled receptors, allostery, conformational changes, docking, protein-protein interactions, Rhodopsin, drug discovery, cytoplasm, GPCR, crystal structure

Abstract: The mammalian dim-light photoreceptor rhodopsin is a prototypic G protein coupled receptor (GPCR), interacting with the G protein, transducin, rhodopsin kinase, and arrestin. All of these proteins interact with rhodopsin at its cytoplasmic surface. Structural and modeling studies have provided in-depth descriptions of the respective interfaces. Overlap and thus competition for binding surfaces is a major regulatory mechanism for signal processing. Recently, it was found that the same surface is also targeted by small molecules. These ligands can directly interfere with the binding and activation of the proteins of the signal transduction cascade, but they can also allosterically modulate the retinal ligand binding pocket. Because the pocket that is targeted contains residues that are highly conserved across Class A GPCRs, these findings imply that it may be possible to target multiple GPCRs with the same ligand(s). This is desirable for example in complex diseases such as cancer where multiple GPCRs participate in the disease networks.

Cite this article as:

Yanamala Naveena, Gardner Eric, Riciutti Alec and Klein-Seetharaman Judith, The Cytoplasmic Rhodopsin-Protein Interface: Potential for Drug Discovery, Current Drug Targets 2012; 13 (1) . https://dx.doi.org/10.2174/138945012798868461