title: A Usual G-Protein-Coupled Receptor in Unusual Membranes.
abstract: G-protein-coupled receptors (GPCRs) are the largest family of membrane-bound receptors and constitute about 50% of all known drug targets. They offer great potential for membrane protein nanotechnologies. We report here a charge-interaction-directed reconstitution mechanism that induces spontaneous insertion of bovine rhodopsin, the eukaryotic GPCR, into both lipid- and polymer-based artificial membranes. We reveal a new allosteric mode of rhodopsin activation incurred by the non-biological membranes: the cationic membrane drives a transition from the inactive MI to the activated MII state in the absence of high [H(+)] or negative spontaneous curvature. We attribute this activation to the attractive charge interaction between the membrane surface and the deprotonated Glu134 residue of the rhodopsin-conserved ERY sequence motif that helps break the cytoplasmic "ionic lock". This study unveils a novel design concept of non-biological membranes to reconstitute and harness GPCR functions in synthetic systems.
authors.affiliation: Department of Chemistry & Biochemistry, Department of Physics University of Arizona, Tucson, AZ 85721 (USA).
authors.forename: Udeep
authors.initials: U
authors.lastname: Chawla
authors.affiliation: Department of Metallurgical & Materials Engineering, Colorado School of Mines, Golden, CO 80401 (USA).|Current address: Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, Texas Tech, University Health Science Center, Lubbock, TX 79430 (USA).
authors.forename: Yunjiang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Metallurgical & Materials Engineering, Colorado School of Mines, Golden, CO 80401 (USA).
authors.forename: Wan
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Metallurgical & Materials Engineering, Colorado School of Mines, Golden, CO 80401 (USA).
authors.forename: Liangju
authors.initials: L
authors.lastname: Kuang
authors.affiliation: Department of Chemistry & Biochemistry, Department of Physics University of Arizona, Tucson, AZ 85721 (USA).
authors.forename: Suchithranga M D C
authors.initials: SM
authors.lastname: Perera
authors.affiliation: Department of Chemistry & Biochemistry, Department of Physics University of Arizona, Tucson, AZ 85721 (USA).
authors.forename: Michael C
authors.initials: MC
authors.lastname: Pitman
authors.affiliation: Department of Chemistry & Biochemistry, Department of Physics University of Arizona, Tucson, AZ 85721 (USA). mfbrown@u.arizona.edu.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Brown
authors.affiliation: Department of Metallurgical & Materials Engineering, Colorado School of Mines, Golden, CO 80401 (USA). H.liang@ttuhsc.edu.|Current address: Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, Texas Tech, University Health Science Center, Lubbock, TX 79430 (USA). H.liang@ttuhsc.edu.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Liang
mesh_terms: D000818:Animals; D002417:Cattle; D002462:Cell Membrane; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000032:analysis*; D053838:Scattering, Small Angle; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D005229:Fatty Acids, Monounsaturated; D000644:Quaternary Ammonium Compounds; D043562:Receptors, G-Protein-Coupled; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane
keywords: G-protein-coupled receptor; biophysics; flexible surface model; photoactivation; rhodopsin