Biochemical and Biophysical Research Communications
Interaction of soluble CD4 with the chemokine receptor CCR5
Section snippets
Materials and methods
Materials. [125I]-MIP-1β and sCD4 were from Perkin–Elmer Life Sciences (Boston, MA). MIP-1β was purchased from Peprotech (Rocky Hill, NJ). Gp120LAI was obtained from Progenics (Tarrytown, NY) and gp120ADA was from Immunodiagnostics (Woburn, MA). The first two-domain fragment of sCD4 (D1D2-sCD4) was kindly provided by Dr. Dimiter Dimitrov.
Cell culture. The human osteosarcoma cell line, transfected with CCR5 (HOS-CCR5), was kindly provided by Dr. Dan Littman. Cells were grown in DMEM containing
Results
It was shown earlier that the two-domain CD4 (D1D2-sCD4) was able to interact with CCR5 and inhibit MIP-1β binding completely, while full-length sCD4 had only little effect. It was suggested that the conformation of the D1D2-fragment of sCD4 exposes a CCR5-interactive region more efficiently than full-length sCD4 [19], [20]. Interestingly, co-expression of CD4 decreases the affinity of CCR5 for its ligand MIP-1β [15]. Since cellular CD4 exists mostly in higher order oligomers, whereas
Discussion
CCR5 and CD4 functionally associate on the plasma membrane and co-expression of CD4 decreases the affinity of CCR5 for MIP-1β [13], [14], [15]. Although full-length sCD4 has little effect on CCR5, its fragment containing only the first two domains interacts efficiently with CCR5 and can inhibit MIP-1β binding completely [13], [19], [20]. Since cellular CD4 exists mostly as homodimers and tetramers and refolded dimeric sCD4 modulates CCR5 potently, we suggest that various conformational forms or
Acknowledgements
This work was supported by a Veterans Affairs Advanced Career Development Award to R.S.
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