title: Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120.
abstract: The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1. To understand the basis of this resistance, we determined co-crystal structures for two poorly neutralizing, CD4-binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120. Both antibodies exhibited approach angles to gp120 similar to those of CD4 and a rare, broadly neutralizing CD4BS antibody, b12. Slight differences in recognition, however, resulted in substantial differences in F105- and b13-bound conformations relative to b12-bound gp120. Modeling and binding experiments revealed these conformations to be poorly compatible with the viral spike. This incompatibility, the consequence of slight differences in CD4BS recognition, renders HIV-1 resistant to all but the most accurately targeted antibodies.
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Lei
authors: L
authors: Chen
authors: Young Do
authors: YD
authors: Kwon
authors: Tongqing
authors: T
authors: Zhou
authors: Xueling
authors: X
authors: Wu
authors: Sijy
authors: S
authors: O'Dell
authors: Lisa
authors: L
authors: Cavacini
authors: Ann J
authors: AJ
authors: Hessell
authors: Marie
authors: M
authors: Pancera
authors: Min
authors: M
authors: Tang
authors: Ling
authors: L
authors: Xu
authors: Zhi-Yong
authors: ZY
authors: Yang
authors: Mei-Yun
authors: MY
authors: Zhang
authors: James
authors: J
authors: Arthos
authors: Dennis R
authors: DR
authors: Burton
authors: Dimiter S
authors: DS
authors: Dimitrov
authors: Gary J
authors: GJ
authors: Nabel
authors: Marshall R
authors: MR
authors: Posner
authors: Joseph
authors: J
authors: Sodroski
authors: Richard
authors: R
authors: Wyatt
authors: John R
authors: JR
authors: Mascola
authors: Peter D
authors: PD
authors: Kwong
mesh_terms: D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D000939:Epitopes; D015483:HIV Antibodies / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D057131:Immune Evasion; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; C514793:gp120 protein, Human immunodeficiency virus 1