7yyk

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<StructureSection load='7yyk' size='340' side='right'caption='[[7yyk]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='7yyk' size='340' side='right'caption='[[7yyk]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7yyk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YYK FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7yyk]] 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=7YYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YYK FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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=7yyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yyk OCA], [https://pdbe.org/7yyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yyk RCSB], [https://www.ebi.ac.uk/pdbsum/7yyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yyk 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=7yyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yyk OCA], [https://pdbe.org/7yyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yyk RCSB], [https://www.ebi.ac.uk/pdbsum/7yyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yyk ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/TSP1_HUMAN TSP1_HUMAN]] Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Binds heparin. May play a role in dentinogenesis and/or maintenance of dentin and dental pulp (By similarity). Ligand for CD36 mediating antiangiogenic properties.<ref>PMID:11134179</ref> <ref>PMID:15014436</ref>
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[[https://www.uniprot.org/uniprot/TSP1_HUMAN TSP1_HUMAN]] Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Binds heparin. May play a role in dentinogenesis and/or maintenance of dentin and dental pulp (By similarity). Ligand for CD36 mediating antiangiogenic properties.<ref>PMID:11134179</ref> <ref>PMID:15014436</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Thrombospondin type-1 repeats (TSRs) are small protein motifs containing six conserved cysteines forming three disulfide bonds that can be modified with an O-linked fucose. Protein O-fucosyltransferase 2 (POFUT2) catalyzes the addition of O-fucose to TSRs containing the appropriate consensus sequence, and the O-fucose modification can be elongated to a Glucose-Fucose disaccharide with the addition of glucose by beta3-glucosyltransferase (B3GLCT). Elimination of Pofut2 in mice results in embryonic lethality in mice, highlighting the biological significance of O-fucose modification on TSRs. Knockout of POFUT2 in HEK293T cells has been shown to cause complete or partial loss of secretion of many proteins containing O-fucosylated TSRs. In addition, POFUT2 is localized to the endoplasmic reticulum (ER) and only modifies folded TSRs, stabilizing their structures. These observations suggest that POFUT2 is involved in an ER quality control mechanism for TSR folding and that B3GLCT also participates in quality control by providing additional stabilization to TSRs. However, the mechanisms by which addition of these sugars result in stabilization are poorly understood. Here, we conducted molecular dynamics (MD) simulations and provide crystallographic and NMR evidence that the Glucose-Fucose disaccharide interacts with specific amino acids in the TSR3 domain in thrombospondin-1 that are within proximity to the O-fucosylation modification site resulting in protection of a nearby disulfide bond. We also show that mutation of these amino acids reduces the stabilizing effect of the sugars in vitro. These data provide mechanistic details regarding the importance of O-fucosylation and how it participates in quality control mechanisms inside the ER.
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O-fucosylation stabilizes the TSR3 motif in thrombospondin-1 by interacting with nearby amino acids and protecting a disulfide bond.,Berardinelli SJ, Eletsky A, Valero-Gonzalez J, Ito A, Manjunath R, Hurtado-Guerrero R, Prestegard JH, Woods RJ, Haltiwanger RS J Biol Chem. 2022 Jun;298(6):102047. doi: 10.1016/j.jbc.2022.102047. Epub 2022, May 18. PMID:35597280<ref>PMID:35597280</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 7yyk" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Berardinelli, S J]]
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[[Category: Berardinelli SJ]]
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[[Category: Eletsky, A]]
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[[Category: Eletsky A]]
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[[Category: Haltiwanger, R S]]
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[[Category: Haltiwanger RS]]
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[[Category: Hurtado-Guerrero, R]]
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[[Category: Hurtado-Guerrero R]]
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[[Category: Ito, A]]
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[[Category: Ito A]]
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[[Category: Manjunath, R]]
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[[Category: Manjunath R]]
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[[Category: Prestegard, J R]]
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[[Category: Prestegard JR]]
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[[Category: Valero-Gonzalez, J]]
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[[Category: Valero-Gonzalez J]]
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[[Category: Woods, R J]]
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[[Category: Woods RJ]]
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[[Category: Cell adhesion]]
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[[Category: O-fucosylation]]
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[[Category: Pofut2]]
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[[Category: Thrombospondin 1]]
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[[Category: Tsr]]
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Revision as of 07:26, 8 September 2022

Crystal structure of the O-fucosylated form of TSRs1-3 from the human thrombospondin 1

PDB ID 7yyk

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