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CCR5 N-terminal reg...
CCR5 N-terminal region plays a critical role in HIV-1 inhibition by Toxoplasma gondii-derived cyclophilin-18
- Article/chapterEnglish2005
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LIBRIS-ID:oai:lup.lub.lu.se:2164f837-0378-45f6-9dd2-47dfa1492a8f
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https://lup.lub.lu.se/record/227517URI
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https://doi.org/10.1074/jbc.M500236200DOI
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Language:English
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Summary in:English
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Molecular mimicry of chemokine ligands has been described for several pathogens. Toxoplasma gondii produces a protein, cyclophilin-18 (C-18), which binds to the human immunodeficiency virus (HIV) co-receptor CCR5 and inhibits fusion and infection of T cells and macrophages by R5 viruses but not by X4 viruses. We recently identified structural determinants of C-18 required for anti-HIV activity (Yarovinsky, F., Andersen, J. F., King, L. R., Caspar, P., Aliberti, J., Golding, H., and Sher, A. ( 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 (Delta 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 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.
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Khurana, S
(author)
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Yarovinsky, F
(author)
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King, L R
(author)
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Abdoulaeva, G
(author)
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Antonsson, LiselotteLund University,Lunds universitet,Drug Target Discovery,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)mphy-lan
(author)
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Owman, ChristerLund University,Lunds universitet,Drug Target Discovery,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)mphy-cow
(author)
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Platt, EJ
(author)
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Kabat, D
(author)
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Andersen, J F
(author)
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Sher, A
(author)
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Drug Target DiscoveryForskargrupper vid Lunds universitet
(creator_code:org_t)
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In:Journal of Biological Chemistry280:33, s. 29570-295771083-351X
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Golding, H
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Khurana, S
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Yarovinsky, F
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King, L R
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Abdoulaeva, G
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Antonsson, Lisel ...
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show more...
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Owman, Christer
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Platt, EJ
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Kabat, D
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Andersen, J F
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Sher, A
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- MEDICAL AND HEALTH SCIENCES
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Lund University