We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Energetic analysis of the rhodopsin-G-protein complex links the α5 helix to GDP release.
- Authors
Alexander, Nathan S; Preininger, Anita M; Kaya, Ali I; Stein, Richard A; Hamm, Heidi E; Meiler, Jens
- 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.
- Subjects
RHODOPSIN; CRYSTAL structure; G proteins; CRYSTALLOGRAPHY; ALLOSTERIC proteins
- Publication
Nature Structural & Molecular Biology, 2014, Vol 21, Issue 1, p56
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2705