The cytoplasmic helix of cannabinoid receptor CB2, a conformational study by circular dichroism and (1)H NMR spectroscopy in aqueous and membrane-like environments.
The cytoplasmic helix domain (fourth cytoplasmic loop, helix 8) of numerous G protein-coupled receptors (GPCRs) such as rhodopsin and the beta-adrenergic receptor exhibit unique structural and functional characteristics. Computer models also predict this structure for the cannabinoid CB2 receptor, another member of the GPCR superfamily. In our study, a peptide corresponding to helix 8 of the CB2 receptor was synthesized chemically and its secondary structure determined by circular dichroism (CD) and (1)H NMR spectroscopy. NMR and CD revealed an alpha-helical structure in this region in both dodecylphosphocholine micelles and dimethylsulfoxide, in contrast to a random coil configuration found in aqueous solvent. This finding is in good agreement with other previous GPCR structural studies including X-ray crystallography. By combining our finding with other studies, we further hypothesize that the amphipathic nature of helix 8 can play a significant role in the function and regulation of CB receptors as well as other GPCRs in general.
Choi
G
G
Institute of Material Science, University of Connecticut, Storrs, USA.
Landin
J
J
Xie
X-Q
XQ
D002942:Circular Dichroism; D003198:Computer Simulation; D003593:Cytoplasm / Q000737:chemistry*; D006801:Humans; D008567:Membranes, Artificial; D008823:Micelles; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D008567:Membranes, Artificial; D008823:Micelles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D014867:Water