CCR5 N-terminal Region Plays a Critical Role in HIV-1 Inhibition byToxoplasma gondii-derived Cyclophilin-18

Hana Golding, Surender Khurana, Felix Yarovinsky, Lisa R. King, Galina Abdoulaeva, Liselotte Antonsson, Christer Owman, Emily J. Platt, David Kabat, John F. Andersen, Alan Sher
2005 Journal of Biological Chemistry  
2004) J. Biol. Chem. 279, 53635-53642). Here we have elucidated the fine specificity of CCR5 residues involved in binding and HIV inhibitory potential of C-18. To delineate the regions of CCR5 involved in C-18 binding, we analyzed C-18 inhibition of cells expressing CXCR4/ CCR5 chimeric receptors and CCR5 with a truncated N terminus (⌬2-19). These experiments identified a critical role for the N terminus of CCR5 in C-18 binding and anti-HIV activity. Studies with a large panel of CCR5
more » ... l of CCR5 N-terminal peptides, including Tyr-sulfated analogues, truncated peptides, and alanine-scanning mutants, suggested that each of the 12-17 amino acids in the N terminus of CCR5 are essential for C-18 binding and inhibitory activity. Tyr sulfation did not improve C-18 reactivity. This finding is of interest because the same CCR5 N-terminal region was shown previously to play a key role in binding of HIV-1 envelope glycoproteins. The elucidation of the functional C-18-binding mechanism may help in the rational design of novel antiviral agents against HIV.
doi:10.1074/jbc.m500236200 pmid:15975927 fatcat:5oakqqt7uzccdjlzhh7wzxnk74