Molecular interactions between the photoreceptor G protein and rhodopsin.
1. The visual transduction system of the vertebrate retina is a well-studied model for biochemical and molecular studies of signal transduction. The structure and function of rhodopsin, a prototypical G protein-coupled receptor, and transducin or Gt, the photoreceptor G protein, have been particularly well studied. Mechanisms of rhodopsin-Gt interaction are discussed in this review. 2. The visual pigment rhodopsin contains a chromophore, and thus conformational changes leading to activation can be monitored spectroscopically. A model of the conformational changes in the activated receptor is presented based on biophysical and biochemical data. 3. The current information on sites of interaction on receptors and cognate G proteins is summarized. Studies using synthetic peptides from amino acid sequences corresponding to Gt and rhodopsin have provided information on the sites of rhodopsin-Gt interaction. Synthetic peptides from the carboxyl terminal region of alpha t mimic Gt by stabilizing the active conformation of rhodopsin, Metarhodopsin II. 4. The conformation of one such peptide when it is bound to Metarhodopsin II was determined by 2D NMR. The model based on the NMR data was tested using peptide analogs predicted to stabilize or break the structure. These studies yield molecular insight into why toxin-treated and mutant G proteins are uncoupled from receptors.
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Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60680.
D000595:Amino Acid Sequence; D000818:Animals; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008027:Light; D008969:Molecular Sequence Data; D010786:Photoreceptor Cells / Q000737:chemistry / Q000502:physiology*; D011487:Protein Conformation; D012243:Rhodopsin / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015293:Transducin / Q000502:physiology
D012243:Rhodopsin; D019204:GTP-Binding Proteins; D015293:Transducin