Energetic analysis of the rhodopsin-G-protein complex links the α5 helix to GDP release

Nat Struct Mol Biol. 2014 Jan;21(1):56-63. doi: 10.1038/nsmb.2705. Epub 2013 Dec 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Electron Spin Resonance Spectroscopy
  • GTP-Binding Proteins / chemistry*
  • Guanosine Diphosphate / chemistry*
  • Models, Molecular
  • Protein Biosynthesis
  • Rhodopsin / chemistry*


  • Guanosine Diphosphate
  • Rhodopsin
  • GTP-Binding Proteins