title: Structural analysis of human and macaque mAbs 2909 and 2.5B: implications for the configuration of the quaternary neutralizing epitope of HIV-1 gp120.
abstract: The quaternary neutralizing epitope (QNE) of HIV-1 gp120 is preferentially expressed on the trimeric envelope spikes of intact HIV virions, and QNE-specific monoclonal antibodies (mAbs) potently neutralize HIV-1. Here, we present the crystal structures of the Fabs of human mAb 2909 and macaque mAb 2.5B. Both mAbs have long beta hairpin CDR H3 regions >20 Å in length that are each situated at the center of their respective antigen-binding sites. Computational analysis showed that the paratopes include the whole CDR H3, while additional CDR residues form shallow binding pockets. Structural modeling suggests a way to understand the configuration of QNEs and the antigen-antibody interaction for QNE mAbs. Our data will be useful in designing immunogens that may elicit potent neutralizing QNE Abs.
authors.affiliation: Department of Biochemistry, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Spurrier
authors.forename: Jared M
authors.initials: JM
authors.lastname: Sampson
authors.forename: Maxim
authors.initials: M
authors.lastname: Totrov
authors.forename: Huiguang
authors.initials: H
authors.lastname: Li
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Neal
authors.forename: Constance
authors.initials: C
authors.lastname: Williams
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Gorny
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: Xiang-Peng
authors.initials: XP
authors.lastname: Kong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D015483:HIV Antibodies / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008251:Macaca / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D020836:Protein Structure, Quaternary
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000956:Antigens, Viral; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120