2n7a: Difference between revisions
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==Solution structure of the human Siglec-8 lectin domain== | |||
<StructureSection load='2n7a' size='340' side='right'caption='[[2n7a]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2n7a]] 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=2N7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N7A 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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2n7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n7a OCA], [https://pdbe.org/2n7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n7a RCSB], [https://www.ebi.ac.uk/pdbsum/2n7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n7a 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. | |||
<div style="background-color:#fffaf0;"> | |||
== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 2n7a" style="background-color:#fffaf0;"></div> | ||
[[Category: Ernst | == References == | ||
[[Category: Proepster | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Schubert | </StructureSection> | ||
[[Category: Yang | [[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]] | |||
Latest revision as of 04:13, 21 November 2024
Solution structure of the human Siglec-8 lectin domainSolution structure of the human Siglec-8 lectin domain
Structural highlights
FunctionSIGL8_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 PubMedSiglec-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. References
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