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5l0r

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human POGLUT1 in complex with Notch1 EGF12 and UDP

Structural highlights

5l0r is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.5Å
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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5l0r"

Categories: Homo sapiens | Large Structures | Li Z | Rini JM

@@ Line 3: / Line 3: @@
 <StructureSection load='5l0r' size='340' side='right'caption='[[5l0r]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5l0r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L0R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L0R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5l0r]] 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=5L0R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L0R FirstGlance]. <br>
-</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 1.5&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[5l0s|5l0s]], [[5l0t|5l0t]], [[5l0u|5l0u]], [[5l0v|5l0v]]</div></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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NOTCH1, TAN1 ([https://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=5l0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l0r OCA], [https://pdbe.org/5l0r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l0r RCSB], [https://www.ebi.ac.uk/pdbsum/5l0r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l0r ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[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. [[https://www.uniprot.org/uniprot/NOTC1_HUMAN NOTC1_HUMAN]] Defects in NOTCH1 are a cause of aortic valve disease 1 (AOVD1) [MIM:[https://omim.org/entry/109730 109730]]. A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome.<ref>PMID:16025100</ref>
+[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 ==
-[[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>  [[https://www.uniprot.org/uniprot/NOTC1_HUMAN NOTC1_HUMAN]] Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. May be important for normal lymphocyte function. In altered form, may contribute to transformation or progression in some T-cell neoplasms. Involved in the maturation of both CD4+ and CD8+ cells in the thymus. May be important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, may function as a receptor for neuronal DNER and may be involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May enhance HIF1A function by sequestering HIF1AN away from HIF1A (By similarity).
+[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;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Li, Z]]
+[[Category: Li Z]]
-[[Category: Rini, J M]]
+[[Category: Rini JM]]
-[[Category: Transferase]]
-[[Category: Transferase glycosyltransferase gt-b glucosyltransferase]]

5l0r

From Proteopedia

Current revision

human POGLUT1 in complex with Notch1 EGF12 and UDP

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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