6r9h: Difference between revisions
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==Crystal structure of the PDZ tandem of syntenin in complex with fragment C58== | ==Crystal structure of the PDZ tandem of syntenin in complex with fragment C58== | ||
<StructureSection load='6r9h' size='340' side='right'caption='[[6r9h]]' scene=''> | <StructureSection load='6r9h' size='340' side='right'caption='[[6r9h]], [[Resolution|resolution]] 2.00Å' 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=6R9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R9H FirstGlance]. <br> | <table><tr><td colspan='2'>[[6r9h]] is a 4 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=6R9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R9H 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=6r9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r9h OCA], [https://pdbe.org/6r9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r9h RCSB], [https://www.ebi.ac.uk/pdbsum/6r9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r9h ProSAT]</span></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]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=JVK:(2~{S})-2-[2-(4-chlorophenyl)sulfanylethanoylamino]-3-methyl-butanoic+acid'>JVK</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6r9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r9h OCA], [https://pdbe.org/6r9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r9h RCSB], [https://www.ebi.ac.uk/pdbsum/6r9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r9h ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/SDCB1_HUMAN SDCB1_HUMAN] Seems to function as an adapter protein. In adherens junctions may function to couple syndecans to cytoskeletal proteins or signaling components. Seems to couple transcription factor SOX4 to the IL-5 receptor (IL5RA). May also play a role in vesicular trafficking. Seems to be required for the targeting of TGFA to the cell surface in the early secretory pathway.<ref>PMID:10230395</ref> <ref>PMID:11179419</ref> <ref>PMID:11498591</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Exosomes support cell-to-cell communication in physiology and disease, including cancer. We currently lack tools, such as small chemicals, capable of modifying exosome composition and activity in a specific manner. Building on our previous understanding of how syntenin, and its PDZ partner syndecan (SDC), impact on exosome composition we optimized a small chemical compound targeting the PDZ2 domain of syntenin. In vitro , in tests on MCF-7 breast carcinoma cells, this compound is non-toxic and impairs cell proliferation, migration and primary sphere formation. It does not affect the size or the number of secreted particles, yet it decreases the amounts of exosomal syntenin, ALIX and SDC4 while leaving other exosomal markers unaffected. Interestingly, it also blocks the sorting of EpCAM, a bona fide target used for carcinoma exosome immunocapture. Our study highlights the first characterization of a small pharmacological inhibitor of the syntenin-exosomal pathway, of potential interest for exosome research and oncology. | |||
Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo.,Leblanc R, Kashyap R, Barral K, Egea-Jimenez AL, Kovalskyy D, Feracci M, Garcia M, Derviaux C, Betzi S, Ghossoub R, Platonov M, Roche P, Morelli X, Hoffer L, Zimmermann P J Extracell Vesicles. 2020 Dec;10(2):e12039. doi: 10.1002/jev2.12039. Epub 2020, Dec 15. PMID:33343836<ref>PMID:33343836</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6r9h" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[3D structures of syntenin|3D structures of syntenin]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Barral K]] | [[Category: Barral K]] | ||
[[Category: Feracci M]] | [[Category: Feracci M]] | ||