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-Structure paper
タイトル | Protein crystallization promotes type 2 immunity and is reversible by antibody treatment. |
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ジャーナル・号・ページ | Science, Vol. 364, Issue 6442, Year 2019 |
掲載日 | 2019年5月24日 |
![]() | Emma K Persson / Kenneth Verstraete / Ines Heyndrickx / Elien Gevaert / Helena Aegerter / Jean-Michel Percier / Kim Deswarte / Koen H G Verschueren / Ann Dansercoer / Delphine Gras / Pascal Chanez / Claus Bachert / Amanda Gonçalves / Hanne Van Gorp / Hans De Haard / Christophe Blanchetot / Michael Saunders / Hamida Hammad / Savvas N Savvides / Bart N Lambrecht / ![]() ![]() ![]() ![]() |
PubMed 要旨 | Although spontaneous protein crystallization is a rare event in vivo, Charcot-Leyden crystals (CLCs) consisting of galectin-10 (Gal10) protein are frequently observed in eosinophilic diseases, such ...Although spontaneous protein crystallization is a rare event in vivo, Charcot-Leyden crystals (CLCs) consisting of galectin-10 (Gal10) protein are frequently observed in eosinophilic diseases, such as asthma. We found that CLCs derived from patients showed crystal packing and Gal10 structure identical to those of Gal10 crystals grown in vitro. When administered to the airways, crystalline Gal10 stimulated innate and adaptive immunity and acted as a type 2 adjuvant. By contrast, a soluble Gal10 mutein was inert. Antibodies directed against key epitopes of the CLC crystallization interface dissolved preexisting CLCs in patient-derived mucus within hours and reversed crystal-driven inflammation, goblet-cell metaplasia, immunoglobulin E (IgE) synthesis, and bronchial hyperreactivity (BHR) in a humanized mouse model of asthma. Thus, protein crystals may promote hallmark features of asthma and are targetable by crystal-dissolving antibodies. |
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手法 | SAS (X-ray synchrotron) / X線回折 |
解像度 | 1.38 - 3.396 Å |
構造データ | ![]() SASDF86: ![]() PDB-6gkq: ![]() PDB-6gks: ![]() PDB-6gkt: ![]() PDB-6gku: ![]() PDB-6glw: ![]() PDB-6glx: ![]() PDB-6qrn: |
化合物 | ![]() ChemComp-GOL: ![]() ChemComp-HOH: ![]() ChemComp-PGE: ![]() ChemComp-PG4: ![]() ChemComp-P6G: ![]() ChemComp-CA: ![]() ChemComp-ACT: ![]() ChemComp-RIP: |
由来 |
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![]() | SUGAR BINDING PROTEIN / Galectin-10 / ex vivo crystal / recombinant / human / Non-autocrystallizing / mutant / Fab / autocrystallizing / crystal solubilisation / IMMUNE SYSTEM / auto-crystallising / complex / carbohydrate-binding / Charcot-Leyden crystal |