A highly conserved arginine in gp120 governs HIV-1 binding to both syndecans and CCR5 via sulfated motifs

Aymeric De Parseval, Michael D. Bobardt, Anju Chatterji, Udayan Chatterji, John H. Elder, Guido David, Susan Zolla-Pazner, Michael Farzan, Tun Hou Lee, Philippe A. Gallay

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


HIV-1 has maximized its utilization of syndecans. It uses them as in cis receptors to infect macrophages and as in trans receptors to infect T-lymphocytes. In this study, we investigated at a molecular level the mechanisms that control HIV-1-syndecan interactions. We found that a single conserved arginine (Arg-298) in the V3 region of gp120 governs HIV-1 binding to syndecans. We found that an amine group on the side chain of this residue is necessary for syndecan utilization by HIV-1. Furthermore, we showed that HIV-1 binds syndecans via a 6-O sulfation, demonstrating that this binding is not the result of random interactions between basic residues and negative charges, but the result of specific contacts between gp120 and a well defined sulfation in syndecans. Surprisingly, we found that Arg-298, which mediates HIV-1 binding to syndecans, also mediates HIV-1 binding to CCR5. We postulated that HIV-1 recognizes similar motifs on syndecans and CCR5. Supporting this hypothesis, we obtained several lines of evidence that suggest that the 6-O sulfation recognized by HIV-1 on syndecans mimics the sulfated tyrosines recognized by HIV-1 in the N terminus of CCR5. Our finding that CCR5 and syndecans are exploited by HIV-1 via a single determinant echoes the mechanisms by which chemokines utilize these two disparate receptors and suggests that the gp120/chemokine mimicry may represent a common strategy in microbial pathogenesis.

Original languageEnglish
Pages (from-to)39493-39504
Number of pages12
JournalJournal of Biological Chemistry
Issue number47
StatePublished - 25 Nov 2005
Externally publishedYes


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