View source for 5vyb


==Structure of the carbohydrate recognition domain of Dectin-2 complexed with a mammalian-type high mannose Man9GlcNAc2 oligosaccharide==
<StructureSection load='5vyb' size='340' side='right'caption='[[5vyb]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vyb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VYB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VYB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=5vyb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vyb OCA], [https://pdbe.org/5vyb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vyb RCSB], [https://www.ebi.ac.uk/pdbsum/5vyb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vyb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CLC6A_HUMAN CLC6A_HUMAN] Binds high-mannose carbohydrates in a Ca(2+)-dependent manner. Functional receptor for alpha-mannans on C.albicans hypheas. Plays an important role in the host defense against C.albicans infection by inducing TH17 cell differentiation. Recognizes also, in a mannose-dependent manner, allergens from house dust mite and fungi, by promoting cysteinyl leukotriene production. Recognizes soluble elements from the eggs of Shistosoma mansoni altering adaptive immune responses. Transduces signals through an Fc receptor gamma chain /FCER1G and Syk-CARD9-NF-kappa-B-dependent pathway (By similarity).
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== Publication Abstract from PubMed ==
Dectin-2, a C-type lectin on macrophages and other cells of the innate immune system, functions in response to pathogens, particularly fungi. The carbohydrate-recognition domain (CRD) in dectin-2 is linked to a transmembrane sequence that interacts with the common Fc receptor gamma subunit to initiate immune signaling. The molecular mechanism by which dectin-2 selectively binds to pathogens has been investigated by characterizing the CRD expressed in a bacterial system. Competition binding studies indicated that the CRD binds to monosaccharides with modest affinity and that affinity was greatly enhanced for mannose-linked alpha1-2 or alpha1-4 to a second mannose residue. Glycan array analysis confirmed selective binding of the CRD to glycans that contain Manalpha1-2Man epitopes. Crystals of the CRD in complex with a mammalian-type high-mannose Man9GlcNAc2 oligosaccharide exhibited interaction with Manalpha1-2Man on two different termini of the glycan, with the reducing-end mannose residue ligated to Ca2+ in a primary binding site and the nonreducing terminal mannose residue occupying an adjacent secondary site. Comparison of the binding sites in DC-SIGN and langerin, two other pathogen-binding receptors of the innate immune system, revealed why these two binding sites accommodate only terminal Manalpha1-2Man structures, whereas dectin-2 can bind Manalpha1-2Man in internal positions in mannans and other polysaccharides. The specificity and geometry of the dectin-2-binding site provide the molecular mechanism for binding of dectin-2 to fungal mannans and also to bacterial lipopolysaccharides, capsular polysaccharides, and lipoarabinomannans that contain the Manalpha1-2Man disaccharide unit.

Mechanism of pathogen recognition by human dectin-2.,Feinberg H, Jegouzo SAF, Rex MJ, Drickamer K, Weis WI, Taylor ME J Biol Chem. 2017 Aug 11;292(32):13402-13414. doi: 10.1074/jbc.M117.799080. Epub , 2017 Jun 26. PMID:28652405<ref>PMID:28652405</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 5vyb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Drickamer K]]
[[Category: Feinberg H]]
[[Category: Jegouzo SAF]]
[[Category: Rex MJ]]
[[Category: Taylor ME]]
[[Category: Weis WI]]