title: Transducin-alpha C-terminal peptide binding site consists of C-D and E-F loops of rhodopsin.
abstract: The binding of heterotrimeric GTP-binding proteins (G-proteins) to serpentine receptors involves several independent contacts. We have deduced the points of interaction between mutant bovine rhodopsins and alphat-(340-350), a peptide corresponding to the C terminus of the alpha subunit (alphat) of bovine retinal G-protein, transducin. Direct binding of alphat-(340-350) to rhodopsin stabilizes the activated metarhodopsin II state (M II), consequently uncoupling the rhodopsin-transducin interaction. This peptide action requires two segments on the cytoplasmic domain of rhodopsin: the Tyr136-Val137-Val138-Val139 sequence on the C-D loop and the Glu247-Lys248-Glu249-Val250-Thr251 sequence on the E-F loop. We propose that a tertiary interaction of these two loop regions forms a pocket for binding the alphat C terminus of the transducin during light transduction in vivo. In most G-proteins, the C termini of alpha subunits are important for interaction with receptors, and, in several serpentine receptors, regions similar to those in rhodopsin are essential for G-protein activation, indicating that the interaction described here may be a generally applicable mode of G-protein binding in signal transduction.
authors.affiliation: Department of Molecular Cardiology, Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195-5069, USA.
authors.forename: S
authors.initials: S
authors.lastname: Acharya
authors.forename: Y
authors.initials: Y
authors.lastname: Saad
authors.forename: S S
authors.initials: SS
authors.lastname: Karnik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003593:Cytoplasm / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000648:ultrastructure; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012243:Rhodopsin / Q000737:chemistry*; D017299:Rod Opsins / Q000235:genetics; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D015293:Transducin / Q000737:chemistry*
chemical_list: D008565:Membrane Proteins; D010455:Peptides; D017299:Rod Opsins; D012243:Rhodopsin; D015293:Transducin