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TitleProtein crystallization promotes type 2 immunity and is reversible by antibody treatment.
Journal, issue, pagesScience, Vol. 364, Issue 6442, Year 2019
Publish dateMay 24, 2019
AuthorsEmma 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 AbstractAlthough 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.
External linksScience / PubMed:31123109
MethodsSAS (X-ray synchrotron) / X-ray diffraction
Resolution1.38 - 3.396 Å
Structure data

SASDF86:
Human Galectin-10 (Tyr69Glu mutant) (Galectin-10 Tyr69Glu, Gal-10)
Method: SAXS/SANS

PDB-6gkq:
X-ray structure determined from ex vivo Charcot-Leyden crystal
Method: X-RAY DIFFRACTION / Resolution: 2.3 Å

PDB-6gks:
X-ray structure determined from recombinant Charcot-Leyden crystal
Method: X-RAY DIFFRACTION / Resolution: 1.38 Å

PDB-6gkt:
X-ray structure of a non-autocrystallizing galectin-10 variant, Gal10-Tyr69Glu
Method: X-RAY DIFFRACTION / Resolution: 2.1 Å

PDB-6gku:
Structure of galectin-10 in complex with the Fab fragment of a Charcot-Leyden crystal solubilizing antibody, 6F5
Method: X-RAY DIFFRACTION / Resolution: 1.91 Å

PDB-6glw:
Structure of galectin-10 in complex with the Fab fragment of a Charcot-Leyden crystal solubilizing antibody, 1D11
Method: X-RAY DIFFRACTION / Resolution: 1.9 Å

PDB-6glx:
Structure of galectin-10 in complex with the Fab fragment of a Charcot-Leyden crystal solubilizing antibody, 4E8
Method: X-RAY DIFFRACTION / Resolution: 3.396 Å

PDB-6qrn:
Galectin-10 complexed with ribose
Method: X-RAY DIFFRACTION / Resolution: 1.4 Å

Chemicals

ChemComp-GOL:
GLYCEROL / Glycerol

ChemComp-HOH:
WATER / Water

ChemComp-PGE:
TRIETHYLENE GLYCOL / Polyethylene glycol

ChemComp-PG4:
TETRAETHYLENE GLYCOL / precipitant*YM / Polyethylene glycol

ChemComp-P6G:
HEXAETHYLENE GLYCOL / precipitant*YM / Polyethylene glycol

ChemComp-CA:
Unknown entry

ChemComp-ACT:
ACETATE ION / Acetate

ChemComp-RIP:
beta-D-ribopyranose / Ribose

Source
  • homo sapiens (human)
  • lama glama (llama)
KeywordsSUGAR 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

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