title: Energetic analysis of the rhodopsin-G-protein complex links the α5 helix to GDP release.
abstract: We present a model of interaction of Gi protein with the activated receptor (R*) rhodopsin, which pinpoints energetic contributions to activation and reconciles the β2 adrenergic receptor-Gs crystal structure with new and previously published experimental data. In silico analysis demonstrated energetic changes when the Gα C-terminal helix (α5) interacts with the R* cytoplasmic pocket, thus leading to displacement of the helical domain and GDP release. The model features a less dramatic domain opening compared with the crystal structure. The α5 helix undergoes a 63° rotation, accompanied by a 5.7-Å translation, that reorganizes interfaces between α5 and α1 helices and between α5 and β6-α5. Changes in the β6-α5 loop displace αG. All of these movements lead to opening of the GDP-binding pocket. The model creates a roadmap for experimental studies of receptor-mediated G-protein activation.
authors.affiliation: 1] Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA. [2].
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Alexander
authors.affiliation: 1] Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA. [2].
authors.forename: Anita M
authors.initials: AM
authors.lastname: Preininger
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Ali I
authors.initials: AI
authors.lastname: Kaya
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Stein
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Hamm
authors.affiliation: 1] Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA. [2] Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Meiler
mesh_terms: D004578:Electron Spin Resonance Spectroscopy; D019204:GTP-Binding Proteins / Q000737:chemistry*; D006153:Guanosine Diphosphate / Q000737:chemistry*; D008958:Models, Molecular; D014176:Protein Biosynthesis; D012243:Rhodopsin / Q000737:chemistry*
chemical_list: D006153:Guanosine Diphosphate; D012243:Rhodopsin; D019204:GTP-Binding Proteins