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| | ==human POGLUT1 in complex with 2F-glucose modified EGF(+) and UDP== | | ==human POGLUT1 in complex with 2F-glucose modified EGF(+) and UDP== |
| - | <StructureSection load='5l0v' size='340' side='right' caption='[[5l0v]], [[Resolution|resolution]] 1.30Å' scene=''> | + | <StructureSection load='5l0v' size='340' side='right'caption='[[5l0v]], [[Resolution|resolution]] 1.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5l0v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L0V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L0V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5l0v]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L0V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L0V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SHG:2-DEOXY-2-FLUORO-BETA-D-GLUCOPYRANOSE'>SHG</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.305Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5l0r|5l0r]], [[5l0s|5l0s]], [[5l0t|5l0t]], [[5l0u|5l0u]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SHG:2-DEOXY-2-FLUORO-BETA-D-GLUCOPYRANOSE'>SHG</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POGLUT1, C3orf9, CLP46, KTELC1, MDSRP, MDS010, UNQ490/PRO1006 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5l0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l0v OCA], [https://pdbe.org/5l0v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l0v RCSB], [https://www.ebi.ac.uk/pdbsum/5l0v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l0v ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5l0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l0v OCA], [http://pdbe.org/5l0v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l0v RCSB], [http://www.ebi.ac.uk/pdbsum/5l0v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l0v ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PGLT1_HUMAN PGLT1_HUMAN]] Dowling-Degos disease. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/PGLT1_HUMAN PGLT1_HUMAN] Dowling-Degos disease. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PGLT1_HUMAN PGLT1_HUMAN]] Dual specificity glycosyltransferase that catalyzes the transfer of glucose and xylose from UDP-glucose and UDP-xylose, respectively, to a serine residue found in the consensus sequence of C-X-S-X-P-C (PubMed:21081508, PubMed:21490058, PubMed:21949356, PubMed:27807076). Specifically targets extracellular EGF repeats of protein such as CRB2, F7, F9 and NOTCH2 (PubMed:21081508, PubMed:21490058, PubMed:21949356, PubMed:27807076). Acts as a positive regulator of Notch signaling by mediating O-glucosylation of Notch, leading to regulate muscle development (PubMed:27807076). Notch glucosylation does not affect Notch ligand binding (PubMed:21490058). Required during early development to promote gastrulation: acts by mediating O-glucosylation of CRB2, which is required for CRB2 localization to the cell membrane (By similarity).[UniProtKB:Q8BYB9]<ref>PMID:21081508</ref> <ref>PMID:21490058</ref> <ref>PMID:21949356</ref> <ref>PMID:27807076</ref> | + | [https://www.uniprot.org/uniprot/PGLT1_HUMAN PGLT1_HUMAN] Dual specificity glycosyltransferase that catalyzes the transfer of glucose and xylose from UDP-glucose and UDP-xylose, respectively, to a serine residue found in the consensus sequence of C-X-S-X-P-C (PubMed:21081508, PubMed:21490058, PubMed:21949356, PubMed:27807076). Specifically targets extracellular EGF repeats of protein such as CRB2, F7, F9 and NOTCH2 (PubMed:21081508, PubMed:21490058, PubMed:21949356, PubMed:27807076). Acts as a positive regulator of Notch signaling by mediating O-glucosylation of Notch, leading to regulate muscle development (PubMed:27807076). Notch glucosylation does not affect Notch ligand binding (PubMed:21490058). Required during early development to promote gastrulation: acts by mediating O-glucosylation of CRB2, which is required for CRB2 localization to the cell membrane (By similarity).[UniProtKB:Q8BYB9]<ref>PMID:21081508</ref> <ref>PMID:21490058</ref> <ref>PMID:21949356</ref> <ref>PMID:27807076</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, Z]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Rini, J M]] | + | [[Category: Li Z]] |
| - | [[Category: Transferase]] | + | [[Category: Rini JM]] |
| - | [[Category: Transferase glycosyltransferase gt-b glucosyltransferase]]
| + | |
| Structural highlights
5l0v is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.305Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
PGLT1_HUMAN Dowling-Degos disease. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
PGLT1_HUMAN Dual specificity glycosyltransferase that catalyzes the transfer of glucose and xylose from UDP-glucose and UDP-xylose, respectively, to a serine residue found in the consensus sequence of C-X-S-X-P-C (PubMed:21081508, PubMed:21490058, PubMed:21949356, PubMed:27807076). Specifically targets extracellular EGF repeats of protein such as CRB2, F7, F9 and NOTCH2 (PubMed:21081508, PubMed:21490058, PubMed:21949356, PubMed:27807076). Acts as a positive regulator of Notch signaling by mediating O-glucosylation of Notch, leading to regulate muscle development (PubMed:27807076). Notch glucosylation does not affect Notch ligand binding (PubMed:21490058). Required during early development to promote gastrulation: acts by mediating O-glucosylation of CRB2, which is required for CRB2 localization to the cell membrane (By similarity).[UniProtKB:Q8BYB9][1] [2] [3] [4]
Publication Abstract from PubMed
Protein O-glucosyltransferase 1/Rumi-mediated glucosylation of Notch epidermal growth factor-like (EGF-like) domains plays an important role in Notch signaling. Protein O-glucosyltransferase 1 shows specificity for folded EGF-like domains, it can only glycosylate serine residues in the C1XSXPC2 motif, and it possesses an uncommon dual donor substrate specificity. Using several EGF-like domains and donor substrate analogs, we have determined the structures of human Protein O-glucosyltransferase 1 substrate/product complexes that provide mechanistic insight into the basis for these properties. Notably, we show that Protein O-glucosyltransferase 1's requirement for folded EGF-like domains also leads to its serine specificity and that two distinct local conformational states are likely responsible for its ability to transfer both glucose and xylose. We also show that Protein O-glucosyltransferase 1 possesses the potential to xylosylate a much broader range of EGF-like domain substrates than was previously thought. Finally, we show that Protein O-glucosyltransferase 1 has co-evolved with EGF-like domains of the type found in Notch.POGLUT1 is a protein-O-glucosyltransferase that transfers glucose and xylose to the EGF-like domains of Notch and other signaling receptors. Here the authors report the structure of human POGLUT1 in complexes with 3 different EGF-like domains and donor substrates and shed light on the enzyme's substrate specificity and catalytic mechanism.
Structural basis of Notch O-glucosylation and O-xylosylation by mammalian protein-O-glucosyltransferase 1 (POGLUT1).,Li Z, Fischer M, Satkunarajah M, Zhou D, Withers SG, Rini JM Nat Commun. 2017 Aug 4;8(1):185. doi: 10.1038/s41467-017-00255-7. PMID:28775322[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wu ZL, Ethen CM, Prather B, Machacek M, Jiang W. Universal phosphatase-coupled glycosyltransferase assay. Glycobiology. 2011 Jun;21(6):727-33. doi: 10.1093/glycob/cwq187. Epub 2010 Nov, 15. PMID:21081508 doi:10.1093/glycob/cwq187
- ↑ Fernandez-Valdivia R, Takeuchi H, Samarghandi A, Lopez M, Leonardi J, Haltiwanger RS, Jafar-Nejad H. Regulation of mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi. Development. 2011 May;138(10):1925-34. doi: 10.1242/dev.060020. Epub 2011 Apr 13. PMID:21490058 doi:http://dx.doi.org/10.1242/dev.060020
- ↑ Takeuchi H, Fernandez-Valdivia RC, Caswell DS, Nita-Lazar A, Rana NA, Garner TP, Weldeghiorghis TK, Macnaughtan MA, Jafar-Nejad H, Haltiwanger RS. Rumi functions as both a protein O-glucosyltransferase and a protein O-xylosyltransferase. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16600-5. doi:, 10.1073/pnas.1109696108. Epub 2011 Sep 26. PMID:21949356 doi:http://dx.doi.org/10.1073/pnas.1109696108
- ↑ Servian-Morilla E, Takeuchi H, Lee TV, Clarimon J, Mavillard F, Area-Gomez E, Rivas E, Nieto-Gonzalez JL, Rivero MC, Cabrera-Serrano M, Gomez-Sanchez L, Martinez-Lopez JA, Estrada B, Marquez C, Morgado Y, Suarez-Calvet X, Pita G, Bigot A, Gallardo E, Fernandez-Chacon R, Hirano M, Haltiwanger RS, Jafar-Nejad H, Paradas C. A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss. EMBO Mol Med. 2016 Nov 2;8(11):1289-1309. doi: 10.15252/emmm.201505815. Print, 2016 Nov. PMID:27807076 doi:http://dx.doi.org/10.15252/emmm.201505815
- ↑ Li Z, Fischer M, Satkunarajah M, Zhou D, Withers SG, Rini JM. Structural basis of Notch O-glucosylation and O-xylosylation by mammalian protein-O-glucosyltransferase 1 (POGLUT1). Nat Commun. 2017 Aug 4;8(1):185. doi: 10.1038/s41467-017-00255-7. PMID:28775322 doi:http://dx.doi.org/10.1038/s41467-017-00255-7
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