Structural highlights
FunctionPublication Abstract from PubMedIPSE/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 IPSEdeltaNLS, a monomeric IPSE/alpha-1 mutant, revealed that IPSE/alpha-1 is a new member of the beta&]gamma]-crystallin superfamily. We demonstrate that this molecule is a general immunoglobulin-binding factor with highest affinity for IgE. NMR binding studies of IPSEdeltaNLS 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. A crystallin fold in the interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE/alpha-1) mediates IgE binding for antigen-independent basophil activation.,Meyer NH, Mayerhofer H, Tripsianes K, Blindow S, Barths D, Mewes A, Weimar T, Kohli T, Bade S, Madl T, Frey A, Haas H, Mueller-Dieckmann J, Sattler M, Schramm G J Biol Chem. 2015 Jul 10. pii: jbc.M115.675066. PMID:26163514[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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