title: Molecular basis for the binding promiscuity of an anti-p24 (HIV-1) monoclonal antibody.
abstract: Multiple binding capabilities utilized by specific protein-to-protein interactions in molecular recognition events are being documented increasingly but remain poorly understood at the molecular level. We identified five unrelated peptides that compete with each other for binding to the paratope region of the monoclonal anti-p24 (HIV-1) antibody CB4-1 by using a synthetic positional scanning combinatorial library XXXX[B1,B2,B3,X1,X2,X3]XXXX (14 mers; 68,590 peptide mixtures in total) prepared by spot synthesis. Complete sets of substitution analogs of the five peptides revealed key interacting residues, information that led to the construction of binding supertopes derived from each peptide. These supertope sequences were identified in hundreds of heterologous proteins, and those proteins that could be obtained were shown to bind CB4-1. Implications of these findings for immune escape mechanisms and autoimmunity are discussed.
authors.affiliation: Institut für Medizinische Immunologie, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kramer
authors.forename: T
authors.initials: T
authors.lastname: Keitel
authors.forename: K
authors.initials: K
authors.lastname: Winkler
authors.forename: W
authors.initials: W
authors.lastname: Stöcklein
authors.forename: W
authors.initials: W
authors.lastname: Höhne
authors.forename: J
authors.initials: J
authors.lastname: Schneider-Mergener
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D004735:Energy Transfer; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies; D016655:HIV Core Protein p24 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D019151:Peptide Library; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D007140:Immunoglobulin Fab Fragments; D009842:Oligopeptides; D019151:Peptide Library