4EL6

Crystal structure of IPSE/alpha-1 from Schistosoma mansoni eggs

4EL6 の概要

• エントリーDOI: 10.2210/pdb4el6/pdb
• 分子名称: IL-4-inducing protein (2 entities in total)
• 機能のキーワード: beta/gamma-crystallin superfamily, triggers il4 release, ige, signaling protein
• 由来する生物種: Schistosoma mansoni (Blood fluke)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11981.48

構造登録者

Mayerhofer, H.,Meyer, H.,Tripsianes, K.,Barths, D.,Blindow, S.,Bade, S.,Madl, T.,Frey, A.,Haas, H.,Sattler, M.,Schramm, G.,Mueller-Dieckmann, J. (登録日: 2012-04-10, 公開日: 2013-04-10, 最終更新日: 2025-05-07)

主引用文献

Meyer, N.H.,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.
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

PubMed 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.

PubMed: 26163514
DOI: 10.1074/jbc.M115.675066

実験手法

X-RAY DIFFRACTION (1.71 Å)