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| | ==Solution structure of the human Siglec-8 lectin domain in complex with 6'sulfo sialyl Lewisx== | | ==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]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2n7b' size='340' side='right'caption='[[2n7b]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2n7b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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> | + | <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='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></td></tr> | + | </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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2n7a|2n7a]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SIGLEC8, SAF2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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> | | <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> | | </table> |
| | == Function == | | == 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.
| + | [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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allain, F H.T]] | + | [[Category: Allain FH-T]] |
| - | [[Category: Ernst, B]] | + | [[Category: Ernst B]] |
| - | [[Category: Proepster, J M]] | + | [[Category: Proepster JM]] |
| - | [[Category: Rabbani, S]] | + | [[Category: Rabbani S]] |
| - | [[Category: Schubert, M]] | + | [[Category: Schubert M]] |
| - | [[Category: Yang, F]] | + | [[Category: Yang F]] |
| - | [[Category: Carbohydrate recognition]]
| + | |
| - | [[Category: Carbohydrate-binding receptor]]
| + | |
| - | [[Category: I-type lectin]]
| + | |
| - | [[Category: Protein-glycan complex]]
| + | |
| - | [[Category: Saf-2]]
| + | |
| - | [[Category: Sialic acid-binding immunoglobulin-like lectin 8]]
| + | |
| - | [[Category: Siglec8]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| - | [[Category: Sulfated sialyl lewis x]]
| + | |
| Structural highlights
2n7b is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | Solution NMR, 20 models |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Propster JM, Yang F, Rabbani S, Ernst B, Allain FH, Schubert M. Structural basis for sulfation-dependent self-glycan recognition by the human immune-inhibitory receptor Siglec-8. 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 doi:http://dx.doi.org/10.1073/pnas.1602214113
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