title: Binding of inositol phosphates to arrestin.
abstract: Arrestin binds to phosphorylated rhodopsin in its light-activated form (metarhodopsin II), blocking thereby its interaction with the G-protein, transducin. In this study, we show that highly phosphorylated forms of inositol compete against the arrestin-rhodopsin interaction. Competition curves and direct binding assays with free arrestin consistently yield affinities in the micromolar range; for example, inositol 1,3,4,5-tetrakisphosphate (InP4) and inositol hexakisphosphate (InP6 bind to arrestin with dissociation constants of 12 microM and 5 microM, respectively. Only a small control amount of inositol phosphates is bound, when arrestin interacts with phosphorylated rhodopsin. This argues for a release of bound inositol phosphates by interaction with rhodopsin. Transducin, rhodopsin kinase, or cyclic GMP phosphodiesterase are not affected by inositol phosphates. These observations open a new way to purify arrestin and to inhibit its interaction with rhodopsin. Their physiological significance deserves further investigation.
authors.affiliation: R.S. Dow Neurological Sciences Institute, Good Samaritan Hospital and Medical Center, Portland, OR 97209.
authors.forename: K
authors.initials: K
authors.lastname: Palczewski
authors.forename: A
authors.initials: A
authors.lastname: Pulvermüller
authors.forename: J
authors.initials: J
authors.lastname: Buczylko
authors.forename: C
authors.initials: C
authors.lastname: Gutmann
authors.forename: K P
authors.initials: KP
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D000941:Antigens / Q000302:isolation & purification / Q000378:metabolism*; D019393:Arrestin; D001667:Binding, Competitive; D002417:Cattle; D005136:Eye Proteins / Q000302:isolation & purification / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding; D012243:Rhodopsin / Q000031:analogs & derivatives* / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000941:Antigens; D019393:Arrestin; D005136:Eye Proteins; D007295:Inositol Phosphates; D008565:Membrane Proteins; C013110:metarhodopsins; D012243:Rhodopsin