Signaling activations through G-protein-coupled-receptor aggregations
Masaki Watabe1, Hideaki Yoshimura2, Satya N V Arjunan1,3
1Laboratory for Biologically Inspired Computing, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka 565-0874, Japan.
Physical Review. E
|October 20, 2020
Summary
This study introduces a new multiary complex model for G-protein-coupled receptor (GPCR) signaling, suggesting receptor aggregation influences cellular responses. The model reveals how receptor oligomers impact ligand binding affinity, especially with low G-protein levels.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Biophysics
Background:
- Eukaryotic cells use extracellular signals via G-protein-coupled receptors (GPCRs), ligands, and G-proteins.
- Existing theories often assume GPCRs exist only as monomers during signaling.
Purpose of the Study:
- To propose a novel multiary complex model for GPCR signaling.
- To investigate the role of unobserved aggregated receptor states in GPCR activation.
- To explore how receptor aggregation affects ligand-receptor binding affinity.
Main Methods:
- Developed a multiary complex model using vector representation for aggregated receptor states.
- Simulated model behavior to analyze GPCR signaling dynamics.
- Examined the influence of receptor oligomerization on binding affinity.
Main Results:
- Receptor aggregation can induce cooperative effects not explained by monomer-based theories.
- Ligand-receptor binding affinity is significantly modulated by receptor oligomer formation.
- These effects are particularly pronounced at low G-protein concentrations.
Conclusions:
- Receptor aggregation is a critical factor in GPCR signaling.
- The proposed multiary complex model offers new insights into GPCR activation mechanisms.
- Understanding receptor aggregation may reveal novel therapeutic targets for signaling modulation.
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