title: A Crystallin Fold in the Interleukin-4-inducing Principle of Schistosoma mansoni Eggs (IPSE/α-1) Mediates IgE Binding for Antigen-independent Basophil Activation.
abstract: The IL-4-inducing principle from Schistosoma mansoni eggs (IPSE/α-1), the major secretory product of eggs from the parasitic worm S. mansoni, efficiently triggers basophils to release the immunomodulatory key cytokine interleukin-4. Activation by IPSE/α-1 requires the presence of IgE on the basophils, but the detailed molecular mechanism underlying activation is unknown. NMR and crystallographic analysis of IPSEΔNLS, a monomeric IPSE/α-1 mutant, revealed that IPSE/α-1 is a new member of the βγ-crystallin superfamily. We demonstrate that this molecule is a general immunoglobulin-binding factor with highest affinity for IgE. NMR binding studies of IPSEΔNLS with the 180-kDa molecule IgE identified a large positively charged binding surface that includes a flexible loop, which is unique to the IPSE/α-1 crystallin fold. Mutational analysis of amino acids in the binding interface showed that residues contributing to IgE binding are important for IgE-dependent activation of basophils. As IPSE/α-1 is unable to cross-link IgE, we propose that this molecule, by taking advantage of its unique IgE-binding crystallin fold, activates basophils by a novel, cross-linking-independent mechanism.
authors.affiliation: From the Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, the Munich Center for Integrated Protein Science and Biomolecular NMR, Department of Chemie, Technische Universität München, 85747 Garching.
authors.forename: N Helge
authors.initials: NH
authors.lastname: Meyer
authors.affiliation: the EMBL Hamburg Outstation ℅ Desy, 22603 Hamburg.
authors.forename: Hubert
authors.initials: H
authors.lastname: Mayerhofer
authors.affiliation: From the Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, the Munich Center for Integrated Protein Science and Biomolecular NMR, Department of Chemie, Technische Universität München, 85747 Garching.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tripsianes
authors.affiliation: the Cellular Allergology and.
authors.forename: Silke
authors.initials: S
authors.lastname: Blindow
authors.affiliation: the Cellular Allergology and.
authors.forename: Daniela
authors.initials: D
authors.lastname: Barths
authors.affiliation: the Cellular Allergology and.
authors.forename: Astrid
authors.initials: A
authors.lastname: Mewes
authors.affiliation: the Institute of Chemistry, University of Lübeck, 23562 Lübeck, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Weimar
authors.affiliation: the Institute of Chemistry, University of Lübeck, 23562 Lübeck, Germany.
authors.forename: Thies
authors.initials: T
authors.lastname: Köhli
authors.affiliation: Mucosal Immunology and Diagnostic Section, Research Center Borstel, 23845 Borstel, and.
authors.forename: Steffen
authors.initials: S
authors.lastname: Bade
authors.affiliation: From the Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, the Munich Center for Integrated Protein Science and Biomolecular NMR, Department of Chemie, Technische Universität München, 85747 Garching.
authors.forename: Tobias
authors.initials: T
authors.lastname: Madl
authors.affiliation: Mucosal Immunology and Diagnostic Section, Research Center Borstel, 23845 Borstel, and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Frey
authors.affiliation: the Cellular Allergology and.
authors.forename: Helmut
authors.initials: H
authors.lastname: Haas
authors.affiliation: the EMBL Hamburg Outstation ℅ Desy, 22603 Hamburg, jochen.mueller-dieckmann@uni-hamburg.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Mueller-Dieckmann
authors.affiliation: From the Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, the Munich Center for Integrated Protein Science and Biomolecular NMR, Department of Chemie, Technische Universität München, 85747 Garching, Sattler@helmholtz-muenchen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Sattler
authors.affiliation: the Cellular Allergology and gschramm@fz-borstel.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schramm
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000947:Antigens, Helminth / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001491:Basophils / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002850:Chromatography, Gel; D003459:Crystallins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004527:Egg Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012550:Schistosoma mansoni / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D000947:Antigens, Helminth; D003459:Crystallins; D004527:Egg Proteins; D015801:Helminth Proteins; C474807:IPSE protein, Schistosoma mansoni; D015847:Interleukin-4; D007073:Immunoglobulin E
keywords: Schistosoma mansoni; basophil; crystal structure; crystallin; interleukin; nuclear magnetic resonance (NMR)