title: Free backbone carbonyls mediate rhodopsin activation.
abstract: Conserved prolines in the transmembrane helices of G-protein-coupled receptors (GPCRs) are often considered to function as hinges that divide the helix into two segments capable of independent motion. Depending on their potential to hydrogen-bond, the free C=O groups associated with these prolines can facilitate conformational flexibility, conformational switching or stabilization of the receptor structure. To address the role of conserved prolines in family A GPCRs through solid-state NMR spectroscopy, we focus on bovine rhodopsin, a GPCR in the visual receptor subfamily. The free backbone C=O groups on helices H5 and H7 stabilize the inactive rhodopsin structure through hydrogen-bonds to residues on adjacent helices. In response to light-induced isomerization of the retinal chromophore, hydrogen-bonding interactions involving these C=O groups are released, thus facilitating repacking of H5 and H7 onto the transmembrane core of the receptor. These results provide insights into the multiple structural and functional roles of prolines in membrane proteins.
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kimata
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Andreyah
authors.initials: A
authors.lastname: Pope
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Omar B
authors.initials: OB
authors.lastname: Sanchez-Reyes
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Eilers
authors.affiliation: School of Biological Sciences, University of Essex, Essex, UK.
authors.forename: Chikwado A
authors.initials: CA
authors.lastname: Opefi
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Martine
authors.initials: M
authors.lastname: Ziliox
authors.affiliation: School of Biological Sciences, University of Essex, Essex, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Reeves
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Steven O
authors.identifier: 0000-0003-1861-7159
authors.initials: SO
authors.lastname: Smith
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D002417:Cattle; D057809:HEK293 Cells; D006801:Humans; D006860:Hydrogen Bonding; D007659:Ketones / Q000737:chemistry; D055537:Light Signal Transduction; D008958:Models, Molecular; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D012243:Rhodopsin / Q000737:chemistry* / Q000502:physiology; D015293:Transducin / Q000737:chemistry
chemical_list: D007659:Ketones; D012243:Rhodopsin; D015293:Transducin