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Binding between a Distal C-Terminus Fragment of Cannabinoid Receptor 1 and Arrestin-2
dc.contributor.author | Singh, Shubhadra | |
dc.contributor.author | Bakashi, Kunal | |
dc.contributor.author | Mercier, Richard W. | |
dc.contributor.author | Makriyannis, Alexandros | |
dc.contributor.author | Pavlopoulos, Spiro | |
dc.date.accessioned | 2017-04-12T20:35:05Z | |
dc.date.available | 2017-04-12T20:35:05Z | |
dc.date.issued | 2011-03-29 | |
dc.identifier.citation | Singh, S., Bakshi, K., Mercier, R. W., Makriyannis, A., & Pavlopoulos, S. (2011). Binding between a Distal C-Terminus Fragment of Cannabinoid Receptor 1 and Arrestin-2. Biochemistry, 50(12), 2223–2234. http://doi.org/10.1021/bi1018144 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23649 | |
dc.description.abstract | Internalization of G-protein coupled receptors is mediated by phosphorylation of the C-terminus, followed by binding with the cytosolic protein arrestin. To explore structural factors that may play a role in internalization of cannabinoid receptor 1 (CB1), we utilize a phosphorylated peptide derived from the distal C-terminus of CB1 (CB15P454-473). Complexes formed between the peptide and human arrestin-2 (wt-arr21-418) were compared to those formed with a truncated arrestin-2 mutant (tr-arr21-382) using isothermal titration calorimetry and nuclear magnetic resonance spectroscopy. The penta-phosphopeptide CB15P454-473 adopts a helix-loop conformation, whether binding to full-length arrestin-2 or its truncated mutant. This structure is similar to that of a hepta-phosphopeptide, mimicking the distal segment of the rhodopsin C-tail (Rh7P330-348), binding to visual arrestin, suggesting that this adopted structure bears functional significance. Isothermal titration calorimetry (ITC) experiments show that the CB15P454-473 peptide binds to tr-arr21-382 with higher affinity than to the full-length wt-arr21-418. As the observed structure of the bound peptides is similar in either case, we attribute the increased affinity to a more exposed binding site on the N-domain of the truncated arrestin construct. The transferred nOe data from the bound phosphopeptides are used to predict a model describing the interaction with arrestin, using the data driven HADDOCK docking program. The truncation of arrestin-2 provides scope for positively charged residues in the polar core of the protein to interact with phosphates present in the loop of the CB15P454-473 peptide. | en_US |
dc.publisher | ACS | en_US |
dc.rights | Copyright © 2011 American Chemical Society | en_US |
dc.title | Binding between a Distal C-Terminus Fragment of Cannabinoid Receptor 1 and Arrestin-2 | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Bakshi, Kunal | |
kusw.kudepartment | Macromolecule and Vaccine Stabilization Centre | en_US |
dc.identifier.doi | 10.1021/bi1018144 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess |