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7au2

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Current revision (05:14, 15 June 2022) (edit) (undo)
 
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==Cryo-EM structure of human exostosin-like 3 (EXTL3)==
==Cryo-EM structure of human exostosin-like 3 (EXTL3)==
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<StructureSection load='7au2' size='340' side='right'caption='[[7au2]]' scene=''>
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<StructureSection load='7au2' size='340' side='right'caption='[[7au2]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AU2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AU2 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7au2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AU2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AU2 FirstGlance]. <br>
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</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=7au2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7au2 OCA], [https://pdbe.org/7au2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7au2 RCSB], [https://www.ebi.ac.uk/pdbsum/7au2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7au2 ProSAT]</span></td></tr>
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</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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glucuronosyl-galactosyl-proteoglycan_4-alpha-N-_acetylglucosaminyltransferase Glucuronosyl-galactosyl-proteoglycan 4-alpha-N- acetylglucosaminyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.223 2.4.1.223] </span></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=7au2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7au2 OCA], [https://pdbe.org/7au2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7au2 RCSB], [https://www.ebi.ac.uk/pdbsum/7au2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7au2 ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[[https://www.uniprot.org/uniprot/EXTL3_HUMAN EXTL3_HUMAN]] Skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome. 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/EXTL3_HUMAN EXTL3_HUMAN]] Glycosyltransferase which regulates the biosynthesis of heparan sulfate (HS). Important for both skeletal development and hematopoiesis, through the formation of HS proteoglycans (HSPGs) (PubMed:28132690, PubMed:28148688). Required for the function of REG3A in regulating keratinocyte proliferation and differentiation (PubMed:22727489).<ref>PMID:22727489</ref> <ref>PMID:28132690</ref> <ref>PMID:28148688</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. Though quickly modified, it is initially synthesised as a polysaccharide of alternating beta-D-glucuronosyl and N-acetyl-alpha-D-glucosaminyl residues by exostosins. These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. We explain the ineffectiveness of EXTL3's GT47 domain to transfer beta-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism.
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The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis.,Wilson LFL, Dendooven T, Hardwick SW, Echevarria-Poza A, Tryfona T, Krogh KBRM, Chirgadze DY, Luisi BF, Logan DT, Mani K, Dupree P Nat Commun. 2022 Jun 8;13(1):3314. doi: 10.1038/s41467-022-31048-2. PMID:35676258<ref>PMID:35676258</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7au2" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Glucuronosyl-galactosyl-proteoglycan 4-alpha-N- acetylglucosaminyltransferase]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Chirgadze DY]]
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[[Category: Chirgadze, D Y]]
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[[Category: Dendooven T]]
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[[Category: Dendooven, T]]
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[[Category: Dupree P]]
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[[Category: Dupree, P]]
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[[Category: Hardwick SW]]
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[[Category: Hardwick, S W]]
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[[Category: Logan DT]]
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[[Category: Logan, D T]]
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[[Category: Luisi BF]]
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[[Category: Luisi, B F]]
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[[Category: Mani K]]
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[[Category: Mani, K]]
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[[Category: Wilson LFL]]
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[[Category: Wilson, L F.L]]
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[[Category: Glycosyltransferase]]
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[[Category: Heparan]]
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[[Category: N-acetylglucosaminyltransferase]]
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[[Category: Transferase]]

Current revision

Cryo-EM structure of human exostosin-like 3 (EXTL3)

PDB ID 7au2

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