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Meyer, N.H. ; Mayerhofer, H.* ; Tripsianes, K. ; Blindow, S.* ; Barths, D.* ; Mewes, A.* ; Weimar, T.* ; Köhli, T.* ; Bade, S.* ; Madl, T. ; Frey, A.* ; Haas, H.* ; Müller-Dieckmann, J.* ; Sattler, M. ; Schramm, G.*

A crystallin fold in the interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE/alpha-1) mediates IgE binding for antigen-independent basophil activation.

J. Biol. Chem. 290, 22111-22126 (2015)
DOI PMC
Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
IPSE/alpha-1, the major secretory product of eggs from the parasitic worm Schistosoma mansoni, efficiently triggers basophils to release the immunomodulatory key cytokine interleukin-4. Activation by IPSE/alpha-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/alpha-1 mutant, revealed that IPSE/alpha-1 is a new member of the β&]gamma]-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/alpha-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/alpha-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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Schistosoma Mansoni ; Basophil ; Crystal Structure ; Crystallin ; Interleukin ; Nuclear Magnetic Resonance (nmr)
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Zeitschrift Journal of Biological Chemistry, The
Quellenangaben Band: 290, Heft: 36, Seiten: 22111-22126 Artikelnummer: , Supplement: ,
Verlag American Society for Biochemistry and Molecular Biology
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)