Helix 8 of the viral chemokine receptor ORF74 directs chemokine binding

D. Verzijl, L.M. Pardo, M.A. van Dijk, Y.K. Gruijthuijsen, A. Jongejan, H. Timmerman, J. Nicholas, M. Schwarz, P.M. Murphy, R. Leurs, M.J. Smit

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Abstract

The constitutively active G-protein-coupled receptor and viral oncogene ORF74, encoded by Kaposi sarcoma-associated herpesvirus (human herpesvirus 8), binds a broad range of chemokines, including CXCL1 (agonist), CXCL8 (neutral ligand), and CXCL10 (inverse agonist). Although chemokines interact with the extracellular N terminus and loops of the receptor, we demonstrate that helix 8 (Hx8) in the intracellular carboxyl tail (C-tail) of ORF74 directs chemokine binding. Partial deletion of the C-tail resulted in a phenotype with reduced constitutive activity but intact regulation by ligands. Complete deletion of the C-tail, including Hx8, resulted in an inactive phenotype that lacks CXCL8 binding sites and has an increased number of binding sites for CXCL10. Similar effects were obtained with the single R7.61
Original languageEnglish
Pages (from-to)35327-35
JournalJournal of Biological Chemistry
Volume281
Issue number46
DOIs
Publication statusPublished - 2006

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