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SHR Neuro Cancer Cardio Lipid Metab Microb

Meyer, NH; Mayerhofer, H; Tripsianes, K; Blindow, S; Barths, D; Mewes, A; Weimar, T; Köhli, T; Bade, S; Madl, T; Frey, A; Haas, H; Mueller-Dieckmann, J; Sattler, M; Schramm, G.
A Crystallin Fold in the Interleukin-4-inducing Principle of Schistosoma mansoni Eggs (IPSE/α-1) Mediates IgE Binding for Antigen-independent Basophil Activation.
J Biol Chem. 2015; 290(36): 22111-22126. Doi: 10.1074/jbc.M115.675066 [OPEN ACCESS]
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Co-authors Med Uni Graz: Madl Tobias
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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. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Find related publications in this database (using NLM MeSH Indexing): Amino Acid Sequence -; Animals -; Antigens, Helminth - chemistry Antigens, Helminth - genetics Antigens, Helminth - metabolism; Basophils - metabolism; Binding Sites - genetics; Blotting, Western -; Chromatography, Gel -; Crystallins - genetics Crystallins - immunology Crystallins - metabolism; Crystallography, X-Ray -; Egg Proteins - chemistry Egg Proteins - genetics Egg Proteins - metabolism; Helminth Proteins - chemistry Helminth Proteins - genetics Helminth Proteins - metabolism; Humans -; Immunoglobulin E - chemistry Immunoglobulin E - metabolism; Interleukin-4 - metabolism; Magnetic Resonance Spectroscopy -; Models, Molecular -; Molecular Sequence Data -; Mutation -; Protein Binding -; Protein Interaction Mapping -; Protein Structure, Secondary -; Protein Structure, Tertiary -; Schistosoma mansoni - genetics Schistosoma mansoni - metabolism; Sequence Homology, Amino Acid -