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| | <StructureSection load='7alj' size='340' side='right'caption='[[7alj]], [[Resolution|resolution]] 1.52Å' scene=''> | | <StructureSection load='7alj' size='340' side='right'caption='[[7alj]], [[Resolution|resolution]] 1.52Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7alj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ALJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ALJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7alj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ALJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ALJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=XYP:BETA-D-XYLOPYRANOSE'>XYP</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]] 1.52Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">N, CG3936 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=XYP:BETA-D-XYLOPYRANOSE'>XYP</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=7alj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7alj OCA], [https://pdbe.org/7alj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7alj RCSB], [https://www.ebi.ac.uk/pdbsum/7alj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7alj 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=7alj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7alj OCA], [https://pdbe.org/7alj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7alj RCSB], [https://www.ebi.ac.uk/pdbsum/7alj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7alj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NOTCH_DROME NOTCH_DROME]] Signaling protein, which regulates, with both positive and negative signals, the differentiation of at least central and peripheral nervous system and eye, wing disk, oogenesis, segmental appendages such as antennae and legs, and muscles, through lateral inhibition or induction. Functions as a receptor for membrane-bound ligands Delta and Serrate to regulate cell-fate determination. Upon ligand activation, and releasing from the cell membrane, the Notch intracellular domain (NICD) forms a transcriptional activator complex with Su(H) (Suppressor of hairless) and activates genes of the E(spl) complex. Essential for proper differentiation of ectoderm. Fringe (fng) acts in the Golgi to determine the type of O-linked fucose on the EGF modules in N, altering the ability of N to bind with Delta (Dl). O-fut1 also has a role in modulating the interaction. Rumi acts in the endoplasmic reticulum to glucosylate the EGF modules in N, this is required for correct folding and cleavage of N.<ref>PMID:10935637</ref> <ref>PMID:18243100</ref>
| + | [https://www.uniprot.org/uniprot/NOTCH_DROME NOTCH_DROME] Signaling protein, which regulates, with both positive and negative signals, the differentiation of at least central and peripheral nervous system and eye, wing disk, oogenesis, segmental appendages such as antennae and legs, and muscles, through lateral inhibition or induction. Functions as a receptor for membrane-bound ligands Delta and Serrate to regulate cell-fate determination. Upon ligand activation, and releasing from the cell membrane, the Notch intracellular domain (NICD) forms a transcriptional activator complex with Su(H) (Suppressor of hairless) and activates genes of the E(spl) complex. Essential for proper differentiation of ectoderm. Fringe (fng) acts in the Golgi to determine the type of O-linked fucose on the EGF modules in N, altering the ability of N to bind with Delta (Dl). O-fut1 also has a role in modulating the interaction. Rumi acts in the endoplasmic reticulum to glucosylate the EGF modules in N, this is required for correct folding and cleavage of N.<ref>PMID:10935637</ref> <ref>PMID:18243100</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: Drome]] | + | [[Category: Drosophila melanogaster]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Johnson, S]] | + | [[Category: Johnson S]] |
| - | [[Category: Lea, S M]] | + | [[Category: Lea SM]] |
| - | [[Category: Suckling, R]] | + | [[Category: Suckling R]] |
| - | [[Category: Notch notch ligand egf domain]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
7alj is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.52Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
NOTCH_DROME Signaling protein, which regulates, with both positive and negative signals, the differentiation of at least central and peripheral nervous system and eye, wing disk, oogenesis, segmental appendages such as antennae and legs, and muscles, through lateral inhibition or induction. Functions as a receptor for membrane-bound ligands Delta and Serrate to regulate cell-fate determination. Upon ligand activation, and releasing from the cell membrane, the Notch intracellular domain (NICD) forms a transcriptional activator complex with Su(H) (Suppressor of hairless) and activates genes of the E(spl) complex. Essential for proper differentiation of ectoderm. Fringe (fng) acts in the Golgi to determine the type of O-linked fucose on the EGF modules in N, altering the ability of N to bind with Delta (Dl). O-fut1 also has a role in modulating the interaction. Rumi acts in the endoplasmic reticulum to glucosylate the EGF modules in N, this is required for correct folding and cleavage of N.[1] [2]
Publication Abstract from PubMed
Accurate Notch signalling is critical for development and homeostasis. Fine-tuning of Notch-ligand interactions has substantial impact on signalling outputs. Recent structural studies have identified a conserved N-terminal C2 domain in human Notch ligands which confers phospholipid binding in vitro. Here, we show that Drosophila ligands Delta and Serrate adopt the same C2 domain structure with analogous variations in the loop regions, including the so-called beta1-2 loop that is involved in phospholipid binding. Mutations in the beta1-2 loop of the Delta C2 domain retain Notch binding but have impaired ability to interact with phospholipids in vitro. To investigate its role in vivo, we deleted five residues within the beta1-2 loop of endogenous Delta. Strikingly, this change compromises ligand function. The modified Delta enhances phenotypes produced by Delta loss-of-function alleles and suppresses that of Notch alleles. As the modified protein is present on the cell surface in normal amounts, these results argue that C2 domain phospholipid binding is necessary for robust signalling in vivo fine-tuning the balance of trans and cis ligand-receptor interactions.
The conserved C2 phospholipid-binding domain in Delta contributes to robust Notch signalling.,Martins T, Meng Y, Korona B, Suckling R, Johnson S, Handford PA, Lea SM, Bray SJ EMBO Rep. 2021 Oct 5;22(10):e52729. doi: 10.15252/embr.202152729. Epub 2021 Aug, 4. PMID:34347930[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bruckner K, Perez L, Clausen H, Cohen S. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature. 2000 Jul 27;406(6794):411-5. PMID:10935637 doi:http://dx.doi.org/10.1038/35019075
- ↑ Acar M, Jafar-Nejad H, Takeuchi H, Rajan A, Ibrani D, Rana NA, Pan H, Haltiwanger RS, Bellen HJ. Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell. 2008 Jan 25;132(2):247-58. doi: 10.1016/j.cell.2007.12.016. PMID:18243100 doi:http://dx.doi.org/10.1016/j.cell.2007.12.016
- ↑ Martins T, Meng Y, Korona B, Suckling R, Johnson S, Handford PA, Lea SM, Bray SJ. The conserved C2 phospholipid-binding domain in Delta contributes to robust Notch signalling. EMBO Rep. 2021 Oct 5;22(10):e52729. doi: 10.15252/embr.202152729. Epub 2021 Aug, 4. PMID:34347930 doi:http://dx.doi.org/10.15252/embr.202152729
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