title: Rhodopsin controls a conformational switch on the transducin gamma subunit.
abstract: Rhodopsin, a prototypical G protein-coupled receptor, catalyzes the activation of a heterotrimeric G protein, transducin, to initiate a visual signaling cascade in photoreceptor cells. The betagamma subunit complex, especially the C-terminal domain of the transducin gamma subunit, Gtgamma(60-71)farnesyl, plays a pivotal role in allosteric regulation of nucleotide exchange on the transducin alpha subunit by light-activated rhodopsin. We report that this domain is unstructured in the presence of an inactive receptor but forms an amphipathic helix upon rhodopsin activation. A K65E/E66K charge reversal mutant of the gamma subunit has diminished interactions with the receptor and fails to adopt the helical conformation. The identification of this conformational switch provides a mechanism for active GPCR utilization of the betagamma complex in signal transfer to G proteins.
authors.affiliation: Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA. kisselev@slu.edu
authors.forename: Oleg G
authors.initials: OG
authors.lastname: Kisselev
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Downs
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017368:Protein Prenylation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D015293:Transducin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D046911:Macromolecular Substances; D010455:Peptides; D021122:Protein Subunits; D012243:Rhodopsin; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin