title: Ligand-binding architecture of human CB2 cannabinoid receptor: evidence for receptor subtype-specific binding motif and modeling GPCR activation.
abstract: The extensive physiological influence of transmission through the CB2 cannabinoid receptor makes this G protein-coupled receptor (GPCR) a promising therapeutic target for treating neuropathic pain, inflammation, and immune disorders. However, there is little direct structural information pertaining to either GPCR or CB2-receptor ligand recognition and activation. The present work helps characterize experimentally the ligand-binding interactions of the human CB2 (hCB2) receptor. This study illustrates how our overall experimental approach, "ligand-assisted protein structure" (LAPS), affords direct determination of the requirements for ligand binding to the hCB2 receptor and discrimination among the binding motifs for ligands that activate therapeutically relevant GPCRs.
authors.affiliation: School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Pei
authors.forename: Richard W
authors.initials: RW
authors.lastname: Mercier
authors.forename: Jenine K
authors.initials: JK
authors.lastname: Anday
authors.forename: Ganesh A
authors.initials: GA
authors.lastname: Thakur
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Zvonok
authors.forename: Dow
authors.initials: D
authors.lastname: Hurst
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Reggio
authors.forename: David R
authors.initials: DR
authors.lastname: Janero
authors.forename: Alexandros
authors.initials: A
authors.lastname: Makriyannis
mesh_terms: D000345:Affinity Labels / Q000378:metabolism; D000595:Amino Acid Sequence; D002460:Cell Line; D055808:Drug Discovery; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D000345:Affinity Labels; D008024:Ligands; D050505:Mutant Proteins; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2