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| Article Authors: | Chih-Chin Huang; Son N Lam; Priyamvada Acharya; Min Tang; Shi-Hua Xiang; Syed Shahzad-Ul Hussan; Robyn L Stanfield; James Robinson; Joseph Sodroski; Ian A Wilson; Richard Wyatt; Carole A Bewley; Peter D Kwong |
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| Article Title: | Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. |
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| Reference ID: | 1019671 |
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| Abstract: | The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (alpha-helix) and 412d (extended loop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system. |
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| Affiliations: | Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. |
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| Date: | 2007 |
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| Reference Type: | Literature |
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| PubMed ID: | 17901336 |
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| Journal: | Science |
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| Journal Volume: | 317 |
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| Article Pages: | 1930-4 |
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| Journal ISSN: | 1095-9203 |
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| Article Chemical List: | Antigens, CD4;HIV Antibodies;HIV Envelope Protein gp120;HIV envelope protein gp120 (305-321);Peptide Fragments;Receptors, CCR5;Sulfates;Tyrosine |
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| Article MeSH List: | Amino Acid Sequence; Antigens, CD4(chemistry; immunology); Crystallography, X-Ray; HIV Antibodies(chemistry; immunology); HIV Envelope Protein gp120(chemistry; immunology; metabolism); HIV-1(metabolism); Humans; Models, Molecular; Molecular Mimicry; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Peptide Fragments(chemistry; metabolism); Receptors, CCR5(chemistry; metabolism); Sulfates(metabolism); Tyrosine(metabolism); Virus Internalization |
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| Curation Last Updated: | 2013-05-28 22:11:09 |
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