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7alk

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Structure of Drosophila C2-DSL-EGF1

Structural highlights

7alk 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 3Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DL_DROME Acts as a ligand for Notch (N) receptor. Essential for proper differentiation of ectoderm. Dl is required for the correct separation of neural and epidermal cell lineages. 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.^[1]

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^[2]

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
↑ 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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7alk"

Categories: Drosophila melanogaster | Large Structures | Johnson S | Lea SM | Suckling R

@@ Line 3: / Line 3: @@
 <StructureSection load='7alk' size='340' side='right'caption='[[7alk]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7alk]] 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=7ALK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ALK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7alk]] 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=7ALK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ALK FirstGlance]. <br>
-</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 3&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dl, CG3619 ([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=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7alk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7alk OCA], [https://pdbe.org/7alk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7alk RCSB], [https://www.ebi.ac.uk/pdbsum/7alk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7alk ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/DL_DROME DL_DROME]] Acts as a ligand for Notch (N) receptor. Essential for proper differentiation of ectoderm. Dl is required for the correct separation of neural and epidermal cell lineages. 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.<ref>PMID:10935637</ref>
+[https://www.uniprot.org/uniprot/DL_DROME DL_DROME] Acts as a ligand for Notch (N) receptor. Essential for proper differentiation of ectoderm. Dl is required for the correct separation of neural and epidermal cell lineages. 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.<ref>PMID:10935637</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Drome]]
+[[Category: Drosophila melanogaster]]
 [[Category: Large Structures]]
-[[Category: Johnson, S]]
+[[Category: Johnson S]]
-[[Category: Lea, S M]]
+[[Category: Lea SM]]
-[[Category: Suckling, R]]
+[[Category: Suckling R]]
-[[Category: Delta notch ligand c2]]
-[[Category: Dsl and egf domain]]
-[[Category: Signaling protein]]

7alk

From Proteopedia

Current revision

Structure of Drosophila C2-DSL-EGF1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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