7zay

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'''Unreleased structure'''
 
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The entry 7zay is ON HOLD until Paper Publication
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==Human heparan sulfate polymerase complex EXT1-EXT2==
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<StructureSection load='7zay' size='340' side='right'caption='[[7zay]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7zay]] is a 2 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=7ZAY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZAY FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7zay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zay OCA], [https://pdbe.org/7zay PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zay RCSB], [https://www.ebi.ac.uk/pdbsum/7zay PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zay ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/EXT1_HUMAN EXT1_HUMAN] Trichorhinophalangeal syndrome type 2;Chondrosarcoma;Multiple osteochondromas. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/EXT1_HUMAN EXT1_HUMAN] Glycosyltransferase forming with EXT2 the heterodimeric heparan sulfate polymerase which catalyzes the elongation of the heparan sulfate glycan backbone (PubMed:10639137, PubMed:22660413, PubMed:36402845, PubMed:36593275, PubMed:9620772). Glycan backbone extension consists in the alternating transfer of (1->4)-beta-D-GlcA and (1->4)-alpha-D-GlcNAc residues from their respective UDP-sugar donors. Both EXT1 and EXT2 are required for the full activity of the polymerase since EXT1 bears the N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity within the complex while EXT2 carries the glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity (PubMed:36402845, PubMed:36593275). Heparan sulfate proteoglycans are ubiquitous components of the extracellular matrix and play an important role in tissue homeostasis and signaling (PubMed:10639137, PubMed:11391482, PubMed:22660413, PubMed:9620772).<ref>PMID:10639137</ref> <ref>PMID:11391482</ref> <ref>PMID:22660413</ref> <ref>PMID:36402845</ref> <ref>PMID:36593275</ref> <ref>PMID:9620772</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Heparan sulfates are complex polysaccharides that mediate the interaction with a broad range of protein ligands at the cell surface. A key step in heparan sulfate biosynthesis is catalyzed by the bi-functional glycosyltransferases EXT1 and EXT2, which generate the glycan backbone consisting of repeating N-acetylglucosamine and glucuronic acid units. The molecular mechanism of heparan sulfate chain polymerization remains, however, unknown. Here, we present the cryo-electron microscopy structure of human EXT1-EXT2, which reveals the formation of a tightly packed hetero-dimeric complex harboring four glycosyltransferase domains. A combination of in vitro and in cellulo mutational studies is used to dissect the functional role of the four catalytic sites. While EXT1 can catalyze both glycosyltransferase reactions, our results indicate that EXT2 might only have N-acetylglucosamine transferase activity. Our findings provide mechanistic insight into heparan sulfate chain elongation as a nonprocessive process and lay the foundation for future studies on EXT1-EXT2 function in health and disease.
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Authors:
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Structure of the human heparan sulfate polymerase complex EXT1-EXT2.,Leisico F, Omeiri J, Le Narvor C, Beaudouin J, Hons M, Fenel D, Schoehn G, Coute Y, Bonnaffe D, Sadir R, Lortat-Jacob H, Wild R Nat Commun. 2022 Nov 19;13(1):7110. doi: 10.1038/s41467-022-34882-6. PMID:36402845<ref>PMID:36402845</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 7zay" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Hons M]]
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[[Category: Leisico F]]
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[[Category: Lortat-Jacob H]]
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[[Category: Omeiri J]]
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[[Category: Schoehn G]]
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[[Category: Wild R]]

Current revision

Human heparan sulfate polymerase complex EXT1-EXT2

PDB ID 7zay

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