The arrestin-bound conformation and dynamics of the phosphorylated carboxy-terminal region of rhodopsin.
Visual arrestin binds to the phosphorylated carboxy-terminal region of rhodopsin to block interactions with transducin and terminate signaling in the rod photoreceptor cells. A synthetic seven-phospho-peptide from the C-terminal region of rhodopsin, Rh(330-348), has been shown to bind arrestin and mimic inhibition of signal transduction. In this study, we examine conformational changes in this synthetic peptide upon binding to arrestin by high-resolution proton nuclear magnetic resonance (NMR). We show that the peptide is completely disordered in solution, but becomes structured upon binding to arrestin. A control, unphosphorylated peptide that fails to bind to arrestin remains highly disordered. Specific NMR distance constraints are used to model the arrestin-bound conformation. The models suggest that the phosphorylated carboxy-terminal region of rhodopsin, Rh(330-348), undergoes significant conformational changes and becomes structured upon binding to arrestin.
Kisselev
Oleg G
OG
Department of Ophthalmology and Biochemistry, Saint Louis University School of Medicine, 1755 S. Grand Blvd., St. Louis, MO 63104, USA. kisselev@slu.edu
McDowell
J Hugh
JH
Hargrave
Paul A
PA
D000818:Animals; D019393:Arrestin / Q000737:chemistry* / Q000378:metabolism*; D002417:Cattle; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction
D019393:Arrestin; D012243:Rhodopsin