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

Alexander NS, Preininger AM, Kaya AI, Stein RA, Hamm HE, Meiler J
Nat Struct Mol Biol. 2014 21 (1): 56-63

PMID: 24292645 · PMCID: PMC3947367 · DOI:10.1038/nsmb.2705

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.

MeSH Terms (6)

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

Connections (3)

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