View source for 2n7b


==Solution structure of the human Siglec-8 lectin domain in complex with 6'sulfo sialyl Lewisx==
<StructureSection load='2n7b' size='340' side='right'caption='[[2n7b]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2n7b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N7B FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0D8:3-AMINOPROPAN-1-OL'>0D8</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=G6S:D-GALACTOSE-6-SULFATE'>G6S</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2n7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n7b OCA], [https://pdbe.org/2n7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n7b RCSB], [https://www.ebi.ac.uk/pdbsum/2n7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n7b ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SIGL8_HUMAN SIGL8_HUMAN] Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3-linked sialic acid. Also binds to alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface.
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== Publication Abstract from PubMed ==
Siglec-8 is a human immune-inhibitory receptor that, when engaged by specific self-glycans, triggers eosinophil apoptosis and inhibits mast cell degranulation, providing an endogenous mechanism to down-regulate immune responses of these central inflammatory effector cells. Here we used solution NMR spectroscopy to dissect the fine specificity of Siglec-8 toward different sialylated and sulfated carbohydrate ligands and determined the structure of the Siglec-8 lectin domain in complex with its prime glycan target 6'-sulfo sialyl Lewis(x) A canonical motif for sialic acid recognition, extended by a secondary motif formed by unique loop regions, recognizing 6-O-sulfated galactose dictates tight specificity distinct from other Siglec family members and any other endogenous glycan recognition receptors. Structure-guided mutagenesis revealed key contacts of both interfaces to be equally essential for binding. Our work provides critical structural and mechanistic insights into how Siglec-8 selectively recognizes its glycan target, rationalizes the functional impact of site-specific glycan sulfation in modulating this lectin-glycan interaction, and will enable the rational design of Siglec-8-targeted agonists to treat eosinophil- and mast cell-related allergic and inflammatory diseases, such as asthma.

Structural basis for sulfation-dependent self-glycan recognition by the human immune-inhibitory receptor Siglec-8.,Propster JM, Yang F, Rabbani S, Ernst B, Allain FH, Schubert M Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):E4170-9. doi:, 10.1073/pnas.1602214113. Epub 2016 Jun 29. PMID:27357658<ref>PMID:27357658</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2n7b" style="background-color:#fffaf0;"></div>

==See Also==
*[[Core-binding factor|Core-binding factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Allain FH-T]]
[[Category: Ernst B]]
[[Category: Proepster JM]]
[[Category: Rabbani S]]
[[Category: Schubert M]]
[[Category: Yang F]]