6r9h

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Crystal structure of the PDZ tandem of syntenin in complex with fragment C58

Structural highlights

6r9h is a 4 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 2Å
Ligands:ACT, JVK, PO4
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2] [3]

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[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
8 reviews cite this structure
Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer.
Han et al. (2022)
7 more
4 other articles
No citations found

See Also

References

  1. ↑ Fernandez-Larrea J, Merlos-Suarez A, Urena JM, Baselga J, Arribas J. A role for a PDZ protein in the early secretory pathway for the targeting of proTGF-alpha to the cell surface. Mol Cell. 1999 Apr;3(4):423-33. PMID:10230395
  2. ↑ Zimmermann P, Tomatis D, Rosas M, Grootjans J, Leenaerts I, Degeest G, Reekmans G, Coomans C, David G. Characterization of syntenin, a syndecan-binding PDZ protein, as a component of cell adhesion sites and microfilaments. Mol Biol Cell. 2001 Feb;12(2):339-50. PMID:11179419
  3. ↑ Geijsen N, Uings IJ, Pals C, Armstrong J, McKinnon M, Raaijmakers JA, Lammers JW, Koenderman L, Coffer PJ. Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein. Science. 2001 Aug 10;293(5532):1136-8. PMID:11498591 doi:http://dx.doi.org/10.1126/science.1059157
  4. ↑ 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. Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo. J Extracell Vesicles. 2020 Dec;10(2):e12039. PMID:33343836 doi:10.1002/jev2.12039

Contents


PDB ID 6r9h

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OCA

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