2n7b: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==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 | <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/ | <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><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> | <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. | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 28: | Line 25: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Allain | [[Category: Allain FH-T]] | ||
[[Category: Ernst | [[Category: Ernst B]] | ||
[[Category: Proepster | [[Category: Proepster JM]] | ||
[[Category: Rabbani | [[Category: Rabbani S]] | ||
[[Category: Schubert | [[Category: Schubert M]] | ||
[[Category: Yang | [[Category: Yang F]] | ||
Revision as of 13:22, 15 March 2023
Solution structure of the human Siglec-8 lectin domain in complex with 6'sulfo sialyl LewisxSolution structure of the human Siglec-8 lectin domain in complex with 6'sulfo sialyl Lewisx
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. See AlsoReferences
|
| ||||||||||||||||