Chemokine-Binding Modulates CXCR4 and CCR5 Receptors Dimerization
Author Information
Author(s): Isik Nilgun, Hereld Dale, Jin Tian
Primary Institution: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Hypothesis
It is unclear whether CXCR4 and CCR5 form heterodimers and whether ligand binding modulates the dimer formation.
Conclusion
CXCR4 and CCR5 spontaneously form heterodimers, and ligand binding causes different conformational changes affecting their dimerization.
Supporting Evidence
- CXCR4 and CCR5 exist as constitutive heterodimers.
- Ligands of CCR5 and CXCR4 induce different conformational changes within these heterodimers.
- Mutations at the C-terminus of CCR5 reduce its ability to form heterodimers with CXCR4.
Takeaway
The study shows that two important receptors in the immune system can stick together and that certain chemicals can change how they fit together.
Methodology
Fluorescence Resonance Energy Transfer (FRET) imaging was used to investigate the formation of CCR5 and CXCR4 heterodimers on live cell membranes.
Limitations
The study was performed using HEK293 cells, and it remains to be determined if the findings apply to actual leukocytes in vivo.
Statistical Information
P-Value
p<0.01
Statistical Significance
p<0.01
Digital Object Identifier (DOI)
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