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==Structure of galectin-10 in complex with the Fab fragment of a Charcot-Leyden crystal solubilizing antibody, 1D11== | |||
<StructureSection load='6glw' size='340' side='right'caption='[[6glw]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6glw]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GLW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GLW FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6gks|6gks]], [[6gkq|6gkq]], [[6gku|6gku]], [[6gkt|6gkt]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6glw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6glw OCA], [http://pdbe.org/6glw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6glw RCSB], [http://www.ebi.ac.uk/pdbsum/6glw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6glw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/LEG10_HUMAN LEG10_HUMAN]] Regulates immune responses through the recognition of cell-surface glycans. Essential for the anergy and suppressive function of CD25-positive regulatory T-cells (Treg).<ref>PMID:17502455</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
Protein crystallization promotes type 2 immunity and is reversible by antibody treatment.,Persson EK, Verstraete K, Heyndrickx I, Gevaert E, Aegerter H, Percier JM, Deswarte K, Verschueren KHG, Dansercoer A, Gras D, Chanez P, Bachert C, Goncalves A, Van Gorp H, De Haard H, Blanchetot C, Saunders M, Hammad H, Savvides SN, Lambrecht BN Science. 2019 May 24;364(6442). pii: 364/6442/eaaw4295. doi:, 10.1126/science.aaw4295. PMID:31123109<ref>PMID:31123109</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6glw" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Savvides, S N]] | |||
[[Category: Verschueren, K]] | |||
[[Category: Verstraete, K]] | |||
[[Category: Autocrystallizing]] | |||
[[Category: Crystal solubilisation]] | |||
[[Category: Fab]] | |||
[[Category: Galectin-10]] | |||
[[Category: Sugar binding protein]] | |||
Revision as of 01:43, 6 June 2019
Structure of galectin-10 in complex with the Fab fragment of a Charcot-Leyden crystal solubilizing antibody, 1D11Structure of galectin-10 in complex with the Fab fragment of a Charcot-Leyden crystal solubilizing antibody, 1D11
Structural highlights
Function[LEG10_HUMAN] Regulates immune responses through the recognition of cell-surface glycans. Essential for the anergy and suppressive function of CD25-positive regulatory T-cells (Treg).[1] Publication Abstract from PubMedAlthough 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. Protein crystallization promotes type 2 immunity and is reversible by antibody treatment.,Persson EK, Verstraete K, Heyndrickx I, Gevaert E, Aegerter H, Percier JM, Deswarte K, Verschueren KHG, Dansercoer A, Gras D, Chanez P, Bachert C, Goncalves A, Van Gorp H, De Haard H, Blanchetot C, Saunders M, Hammad H, Savvides SN, Lambrecht BN Science. 2019 May 24;364(6442). pii: 364/6442/eaaw4295. doi:, 10.1126/science.aaw4295. PMID:31123109[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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