title: Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4.
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.
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Chih-Chin
authors: CC
authors: Huang
authors: Son N
authors: SN
authors: Lam
authors: Priyamvada
authors: P
authors: Acharya
authors: Min
authors: M
authors: Tang
authors: Shi-Hua
authors: SH
authors: Xiang
authors: Syed Shahzad-Ul
authors: SS
authors: Hussan
authors: Robyn L
authors: RL
authors: Stanfield
authors: James
authors: J
authors: Robinson
authors: Joseph
authors: J
authors: Sodroski
authors: Ian A
authors: IA
authors: Wilson
authors: Richard
authors: R
authors: Wyatt
authors: Carole A
authors: CA
authors: Bewley
authors: Peter D
authors: PD
authors: Kwong
mesh_terms: D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000737:chemistry* / Q000276:immunology; D018360:Crystallography, X-Ray; D015483:HIV Antibodies / Q000737:chemistry* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D019713:Receptors, CCR5 / Q000737:chemistry* / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D013431:Sulfates; D014443:Tyrosine