5lc4
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Xray structure of mouse FAM3C ILEI dimer== | |
| + | <StructureSection load='5lc4' size='340' side='right'caption='[[5lc4]], [[Resolution|resolution]] 1.84Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5lc4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LC4 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.84Å</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=5lc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lc4 OCA], [https://pdbe.org/5lc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lc4 RCSB], [https://www.ebi.ac.uk/pdbsum/5lc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lc4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FAM3C_MOUSE FAM3C_MOUSE] May be involved in retinal laminar formation. Promotes epithelial to mesenchymal transition.<ref>PMID:16959614</ref> <ref>PMID:19015638</ref> <ref>PMID:20059962</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Production and secretion of pro-metastatic proteins is a feature of many tumor cells. The FAM3C Interleukin-like epithelial-to-mesenchymal-transition (EMT) inducer, ILEI has been shown to be strongly up-regulated in several cancers and to be essential for tumor formation and metastasis in epithelial cells, correlating with a significant decrease in overall survival in colon and breast cancer patients. ILEI has been seen to interact with the gamma-secretase presenilin 1 subunit (PS1). However, not much is known about the mechanism-of-action or the detailed ILEI structure. We here present the crystal structures of FAM3C ILEI and show that it exists as monomers but also as covalent dimers. The observed ILEI beta-beta-alpha fold confirmed previous indications that the FAM3C proteins do not form classical four-helix-bundle structures as was initially predicted. This provides the first experimental evidence that the Interleukin-like EMT-inducers are not evolutionarily related to the interleukins. However, more surprisingly the ILEI dimer structure was found to feature a trans-linked domain swap, converting an intramolecular disulfide to intermolecular. Interestingly, dimeric but not monomeric ILEI was subsequently found to cause a dose-dependent increase in EpRas cell invasiveness comparable to TGF-beta, indicating that the dimer might be the active ILEI species. This is in line with a parallel study showing that covalent oligomerization of ILEI is essential for EMT and tumor progression in vivo. The structures and the activity data gives some first insight into the relationship between dimerization and ILEI function as well as indicate an intriguing link between ILEI, the PS1-protease, TGF-beta and the TGF-beta receptor 1. | ||
| - | + | The interleukin-like epithelial-mesenchymal transition inducer ILEI exhibits a non-interleukin-like fold and is active as a domain-swapped dimer.,Jansson AM, Csiszar A, Maier J, Nystrom AC, Ax E, Johansson P, Holmberg Schiavone L J Biol Chem. 2017 Jul 27. pii: jbc.M117.782904. doi: 10.1074/jbc.M117.782904. PMID:28751379<ref>PMID:28751379</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Jansson | + | <div class="pdbe-citations 5lc4" style="background-color:#fffaf0;"></div> |
| - | [[Category: Johansson | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Jansson A]] | ||
| + | [[Category: Johansson P]] | ||
Current revision
Xray structure of mouse FAM3C ILEI dimer
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