title: Structure of a human IgA1 Fab fragment at 1.55 Å resolution: potential effect of the constant domains on antigen-affinity modulation.
abstract: Despite being the most abundant class of immunoglobulins in humans and playing central roles in the adaptive immune response, high-resolution structural data are still lacking for the antigen-binding region of human isotype A antibodies (IgAs). The crystal structures of a human Fab fragment of IgA1 in three different crystal forms are now reported. The three-dimensional organization is similar to those of other Fab classes, but FabA1 seems to be more rigid, being constrained by a hydrophobic core in the interface between the variable and constant domains of the heavy chain (VH-CH1) as well as by a disulfide bridge that connects the light and heavy chains, influencing the relative heavy/light-chain orientation. The crystal structure of the same antibody but with a G-isotype CH1 which is reported to display different antigen affinity has also been solved. The differential structural features reveal plausible mechanisms for constant/variable-domain long-distance effects whereby antibody class switching could alter antigen affinity.
authors.affiliation: Unit of Recombinant Proteins, Institut Pasteur de Montevideo, 11400 Montevideo, Uruguay.
authors.forename: Agustin
authors.initials: A
authors.lastname: Correa
authors.forename: Felipe
authors.initials: F
authors.lastname: Trajtenberg
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Obal
authors.forename: Otto
authors.initials: O
authors.lastname: Pritsch
authors.forename: Guillermo
authors.initials: G
authors.lastname: Dighiero
authors.forename: Pablo
authors.initials: P
authors.lastname: Oppezzo
authors.forename: Alejandro
authors.initials: A
authors.lastname: Buschiazzo
mesh_terms: D000937:Antigen-Antibody Reactions / Q000502:physiology; D000941:Antigens / Q000737:chemistry* / Q000502:physiology; D001666:Binding Sites, Antibody; D003013:Clostridium / Q000201:enzymology; D018360:Crystallography, X-Ray; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry* / Q000502:physiology; D007127:Immunoglobulin Constant Regions / Q000737:chemistry* / Q000502:physiology; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000502:physiology; D009344:Neisseria gonorrhoeae / Q000201:enzymology; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000502:physiology
chemical_list: D000941:Antigens; D007070:Immunoglobulin A; D007127:Immunoglobulin Constant Regions; D007140:Immunoglobulin Fab Fragments; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase
keywords: antibodies; antigen-affinity control; human IgA; protein conformational entropy