title: Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01.
abstract: During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Tongqing
authors.initials: T
authors.lastname: Zhou
authors.forename: Ivelin
authors.initials: I
authors.lastname: Georgiev
authors.forename: Xueling
authors.initials: X
authors.lastname: Wu
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.forename: Kaifan
authors.initials: K
authors.lastname: Dai
authors.forename: Andrés
authors.initials: A
authors.lastname: Finzi
authors.forename: Young Do
authors.initials: YD
authors.lastname: Kwon
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Scheid
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yang
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shapiro
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
mesh_terms: D016915:AIDS Vaccines; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000276:immunology*; D000915:Antibody Affinity; D000940:Antigenic Variation; D001483:Base Sequence; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000737:chemistry* / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments; C514793:gp120 protein, Human immunodeficiency virus 1