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Synergetic Roles of Formyl Peptide Receptor 1 Oligomerization in Ligand-Induced Signal Transduction
- Source :
- ACS Chemical Biology. 15:2577-2587
- Publication Year :
- 2020
- Publisher :
- American Chemical Society (ACS), 2020.
-
Abstract
- G protein-coupled receptors (GPCRs) transduce extracellular signals into cells by interacting with G proteins and arrestins. Emerging evidence suggests that GPCRs on the plasma membrane are in a dynamic equilibrium among monomers, dimers, and larger oligomers. Nevertheless, the role of the oligomer formation in the GPCR signal transduction remains unclear. Using multicolor single-molecule live-cell imaging, we show a dynamic interconversion between small and large oligomer states of a chemoattractant GPCR, Formyl Peptide Receptor 1 (FPR1), and its binding affinity with G protein. Full agonist stimulation increased a fraction of large FPR1 oligomers, which allowed for prolonged FPR1-G protein interaction. The G protein interaction with FPR1 was most stabilized at the full agonist-bound large FPR1 oligomers. Based on these results, we propose that G protein-mediated signal transduction may be regulated synergistically by the ligand-binding and FPR1 oligomerization. Cooperative signal control induced by receptor oligomerization is anticipated as a target for drug discovery.
- Subjects :
- 0301 basic medicine
G protein
Ligands
01 natural sciences
Biochemistry
Oligomer
Formyl peptide receptor 1
03 medical and health sciences
chemistry.chemical_compound
GTP-Binding Proteins
Humans
Receptor
Fluorescent Dyes
G protein-coupled receptor
010405 organic chemistry
Chemistry
Drug discovery
General Medicine
Ligand (biochemistry)
Receptors, Formyl Peptide
0104 chemical sciences
HEK293 Cells
030104 developmental biology
Microscopy, Fluorescence
Biophysics
Molecular Medicine
Protein Multimerization
Single-Cell Analysis
Signal transduction
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 15548937 and 15548929
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- ACS Chemical Biology
- Accession number :
- edsair.doi.dedup.....72c264fd01d5b361733c49a1121bfcc8