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==Structure of Drosophila Serrate C2-DSL-EGF1-EGF2== | ==Structure of Drosophila Serrate C2-DSL-EGF1-EGF2== | ||
<StructureSection load='7alt' size='340' side='right'caption='[[7alt]]' scene=''> | <StructureSection load='7alt' size='340' side='right'caption='[[7alt]], [[Resolution|resolution]] 2.03Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ALT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ALT FirstGlance]. <br> | <table><tr><td colspan='2'>[[7alt]] is a 2 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=7ALT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ALT FirstGlance]. <br> | ||
</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=7alt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7alt OCA], [https://pdbe.org/7alt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7alt RCSB], [https://www.ebi.ac.uk/pdbsum/7alt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7alt ProSAT]</span></td></tr> | </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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ser, Bd, CG6127 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</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=7alt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7alt OCA], [https://pdbe.org/7alt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7alt RCSB], [https://www.ebi.ac.uk/pdbsum/7alt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7alt ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/SERR_DROME SERR_DROME]] Acts as a ligand for Notch (N) receptor. Essential for proper ectodermal development. Serrate represents an element in a network of interacting molecules operating at the cell surface during the differentiation of certain tissues. | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:34347930</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7alt" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Drome]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Johnson S]] | [[Category: Johnson, S]] | ||
[[Category: Lea | [[Category: Lea, S M]] | ||
[[Category: Suckling R]] | [[Category: Suckling, R]] | ||
[[Category: Dsl and egf domain]] | |||
[[Category: Serrate notch ligand c2]] | |||
[[Category: Signaling protein]] | |||
Revision as of 15:48, 13 October 2021
Structure of Drosophila Serrate C2-DSL-EGF1-EGF2Structure of Drosophila Serrate C2-DSL-EGF1-EGF2
Structural highlights
Function[SERR_DROME] Acts as a ligand for Notch (N) receptor. Essential for proper ectodermal development. Serrate represents an element in a network of interacting molecules operating at the cell surface during the differentiation of certain tissues. Publication Abstract from PubMedAccurate 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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