Platelet Factor 4 and Interleukin-8 CXC Chemokine Heterodimer Formation Modulates Function at the Quaternary Structural Level
| Autor: | Arjan W. Griffioen, Guoping Wu, Frank Mortari, Loes I. van Eijk, Yuk Y. Sham, Arne Slungaard, Arkadiusz Z. Dudek, Irina V. Nesmelova, Kevin H. Mayo |
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| Rok vydání: | 2005 |
| Předmět: |
Umbilical Veins
Magnetic Resonance Spectroscopy Protein Conformation Genetic Vectors Biology Platelet Factor 4 Transfection CXCR3 Biochemistry Protein Structure Secondary Receptors Interleukin-8B Receptors Interleukin-8A Diffusion Mice Chemokine receptor Cell Movement Animals Humans Endothelium CXC chemokine receptors Protein Structure Quaternary CXCL14 Molecular Biology Cells Cultured CXCL16 Cell Proliferation Dose-Response Relationship Drug Chemotaxis Interleukin-8 Cell Biology Protein Structure Tertiary Cell biology Kinetics Models Chemical Cytokines XCL2 CXCL9 Chemokines Chemokines CXC Dimerization Protein Binding CCL21 |
| Zdroj: | Journal of Biological Chemistry. 280:4948-4958 |
| ISSN: | 0021-9258 |
| Popis: | The apparent complexity of biology increases as more biomolecular interactions that mediate function become known. We have used NMR spectroscopy and molecular modeling to provide direct evidence that tetrameric platelet factor-4 (PF4) and dimeric interleukin-8 (IL8), two members of the CXC chemokine family, readily interact by exchanging subunits and forming heterodimers via extension of their antiparallel beta-sheet domains. We further demonstrate using functional assays that PF4/IL8 heterodimerization has a direct and significant consequence on the biological activity of both chemokines. Formation of heterodimers enhances the anti-proliferative effect of PF4 on endothelial cells in culture, as well as the IL8-induced migration of CXCR2 vector-transfected Baf3 cells. These results suggest that CXC chemokine biology, and perhaps cytokine biology in general, may be functionally modulated at the molecular level by formation of heterodimers. This concept, in turn, has implications for designing chemokine/cytokine variants with modified biological properties. |
| Databáze: | OpenAIRE |
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