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Fluorescence Resonance Energy Transfer Imaging Reveals that Chemokine-Binding Modulates Heterodimers of CXCR4 and CCR5 Receptors
- Source :
- PLoS ONE, PLoS ONE, Vol 3, Iss 10, p e3424 (2008)
- Publication Year :
- 2008
- Publisher :
- Public Library of Science, 2008.
-
Abstract
- Background Dimerization has emerged as an important feature of chemokine G-protein-coupled receptors. CXCR4 and CCR5 regulate leukocyte chemotaxis and also serve as a co-receptor for HIV entry. Both receptors are recruited to the immunological synapse during T-cell activation. However, it is not clear whether they form heterodimers and whether ligand binding modulates the dimer formation. Methodology/Principal Findings Using a sensitive Fluorescence Resonance Energy Transfer (FRET) imaging method, we investigated the formation of CCR5 and CXCR4 heterodimers on the plasma membrane of live cells. We found that CCR5 and CXCR4 exist as constitutive heterodimers and ligands of CCR5 and CXCR4 promote different conformational changes within these preexisting heterodimers. Ligands of CCR5, in contrast to a ligand of CXCR4, induced a clear increase in FRET efficiency, indicating that selective ligands promote and stabilize a distinct conformation of the heterodimers. We also found that mutations at C-terminus of CCR5 reduced its ability to form heterodimers with CXCR4. In addition, ligands induce different conformational transitions of heterodimers of CXCR4 and CCR5 or CCR5STA and CCR5Δ4. Conclusions/Significance Taken together, our data suggest a model in which CXCR4 and CCR5 spontaneously form heterodimers and ligand-binding to CXCR4 or CCR5 causes different conformational changes affecting heterodimerization, indicating the complexity of regulation of dimerization/function of these chemokine receptors by ligand binding.
- Subjects :
- Chemokine
Receptors, CXCR4
Receptors, CCR5
Protein Conformation
viruses
lcsh:Medicine
Plasma protein binding
Ligands
Cell Biology/Cell Signaling
Cell Line
Chemokine receptor
Immunology/Leukocyte Signaling and Gene Expression
Cell Biology/Cytoskeleton
Fluorescence Resonance Energy Transfer
Humans
lcsh:Science
Receptor
Multidisciplinary
biology
lcsh:R
virus diseases
Ligand (biochemistry)
Förster resonance energy transfer
Chemokine binding
Biochemistry
Liver
Microscopy, Fluorescence
Immunology/Leukocyte Activation
biology.protein
Biophysics
lcsh:Q
Chemokines
Dimerization
Leukocyte chemotaxis
Research Article
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 3
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....fbcffcb28e59b1cab08e7f3b067e7c70