Structures of the CCR5 N Terminus and of a Tyrosine-Sulfated Antibody with HIV-1 gp120 and CD4

• Published in: Science (American Association for the Advancement of Science) Vol. 317; no. 5846; pp. 1930 - 1934
• Main Authors: Huang, Chih-chin, Lam, Son N., Acharya, Priyamvada, Tang, Min, Xiang, Shi-Hua, Hussan, Syed Shahzad-ul, Stanfield, Robyn L., Robinson, James, Sodroski, Joseph, Wilson, Ian A., Wyatt, Richard, Bewley, Carole A., Kwong, Peter D.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 28-09-2007; The American Association for the Advancement of Science
• Subjects: AIDS; Amino Acid Sequence; Antibodies; Binding sites; Biological and medical sciences; Biomedical research; CD4 Antigens - chemistry; CD4 Antigens - immunology; Cellular biology; Crystal structure; Crystallography, X-Ray; Crystals; Fundamental and applied biological sciences. Psychology; Glycoproteins; HIV; HIV 1; HIV Antibodies - chemistry; HIV Antibodies - immunology; HIV Envelope Protein gp120 - chemistry; HIV Envelope Protein gp120 - immunology; HIV Envelope Protein gp120 - metabolism; HIV-1 - metabolism; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Hydrogen bonds; Immunology; Models, Molecular; Molecular biophysics; Molecular Mimicry; Molecular Sequence Data; Molecular structure; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Receptors; Receptors, CCR5 - chemistry; Receptors, CCR5 - metabolism; Structure in molecular biology; Sulfates; Sulfates - metabolism; Tridimensional structure; Tyrosine - metabolism; Virus Internalization; Virus; CCR5 chemokine receptor; Tyrosine; Three dimensional structure; Antibody; N terminal-Sequence; Retroviridae; Coat protein; Human immunodeficiency virus; Lentivirus; Sulfatation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1145373

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 (α-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.