Interaction of a fragment of the cannabinoid CB1 receptor C-terminus with arrestin-2.
Desensitization of the cannabinoid CB1 receptor is mediated by the interaction with arrestin. In this study, we report the structural changes of a synthetic diphosphorylated peptide corresponding to residues 419-439 of the CB1 C-terminus upon binding to arrestin-2. This segment is pivotal to the desensitization of CB1. Using high-resolution proton NMR, we observe two helical segments in the bound peptide that are separated by the presence a glycine residue. The binding we observe is with a diphoshorylated peptide, whereas a previous study reported binding of a highly phosphorylated rhodopsin fragment to visual arrestin. The arrestin bound conformations of the peptides are compared.
Bakshi
Kunal
K
Department of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Road, U-3092, Storrs, CT 06269, USA.
Mercier
Richard W
RW
Pavlopoulos
Spiro
S
D000595:Amino Acid Sequence; D019390:Arrestins / Q000737:chemistry*; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry*; D000071557:beta-Arrestins
D019390:Arrestins; D010455:Peptides; D043884:Receptor, Cannabinoid, CB1; D000071557:beta-Arrestins