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Updated: Jul 14, 2026
09:12
G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
Published on: September 10, 2016
Protein Frustration Reveals Orthosteric and Allosteric Active Sites in GPCR:G Protein Complexes
Wenyuan Wei1,2, Roland Del Mundo1,2, Tianyi Yang1
1Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, 1218 S 5th Ave, Monrovia, California 91016, United States.
Journal of Chemical Information and Modeling
|July 13, 2026
Summary
Protein structural frustration, a suboptimal energy state, is concentrated at G protein-coupled receptor (GPCR) interfaces. This frustration also appears on Gα subunits at effector binding sites, aiding interface identification.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Protein structures typically adopt optimal energy states for stability.
- However, functionally critical amino acid residues can exhibit
Purpose of the Study:
- To investigate the role of protein frustration in G protein-coupled receptors (GPCRs) and their interactions.
- To determine if frustrated residues identify functional interfaces.
Main Methods:
- Analysis of over 1200 three-dimensional structures of GPCRs.
- Mapping residue frustration density across receptor structures and G protein subunits.
Main Results:
- Residues at GPCR-ligand and GPCR-G protein interfaces show higher frustration density.
- The Gα subunit exhibits frustrated residue clusters at effector protein binding sites (Gbγ, RGS, Adenylyl cyclase, Ric8).
Conclusions:
- Protein frustration is a key structural property for identifying protein-protein interaction interfaces.
- Frustration analysis can prospectively predict ligand binding sites on GPCRs and G proteins.
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