7bqg
From Proteopedia
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==Complex structure of SAV1 and Dendrin== | ==Complex structure of SAV1 and Dendrin== | ||
| - | <StructureSection load='7bqg' size='340' side='right'caption='[[7bqg]]' scene=''> | + | <StructureSection load='7bqg' size='340' side='right'caption='[[7bqg]], [[Resolution|resolution]] 1.55Å' 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=7BQG OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[7bqg]] is a 1 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=7BQG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BQG FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5501087Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</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=7bqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bqg OCA], [https://pdbe.org/7bqg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bqg RCSB], [https://www.ebi.ac.uk/pdbsum/7bqg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bqg ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SAV1_MOUSE SAV1_MOUSE] Regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. SAV1 is required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle exit and terminal differentiation in developing epithelial tissues. Plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with STK3/MST2, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation (By similarity).<ref>PMID:18369314</ref> <ref>PMID:20080689</ref> [https://www.uniprot.org/uniprot/DEND_MOUSE DEND_MOUSE] Promotes apoptosis of kidney glomerular podocytes. Podocytes are highly specialized cells essential to the ultrafiltration of blood, resulting in the extraction of urine and the retention of protein.<ref>PMID:17537921</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The canonical mammalian Hippo pathway contains a core kinase signaling cascade requiring upstream MST to form a stable complex with SAV1 in order to phosphorylate the downstream LATS/MOB complex. Though SAV1 dimerization is essential for the trans-activation of MST, the molecular mechanism underlying SAV1 dimerization is unclear. Here, we discover that the SAV1 WW tandem containing a short Pro-rich extension immediately following the WW tandem (termed as "WW12ex") forms a highly stable homodimer. The crystal structure of SAV1 WW12ex reveals that the Pro-rich extension of one subunit binds to both WW domains from the other subunit. Thus, SAV1 WW12ex forms a domain-swapped dimer instead of a WW2 homodimerization-mediated dimer. The WW12ex-mediated dimerization of SAV1 is required for the MST/SAV1 complex assembly and MST kinase activation. Finally, we show that several cancer-related SAV1 variants disrupt SAV1 dimer formation, and thus, these mutations may impair the tumor-suppression activity of SAV1. | ||
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| + | A WW Tandem-Mediated Dimerization Mode of SAV1 Essential for Hippo Signaling.,Lin Z, Xie R, Guan K, Zhang M Cell Rep. 2020 Sep 8;32(10):108118. doi: 10.1016/j.celrep.2020.108118. PMID:32905778<ref>PMID:32905778</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7bqg" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
[[Category: Lin Z]] | [[Category: Lin Z]] | ||
[[Category: Zhang M]] | [[Category: Zhang M]] | ||
Current revision
Complex structure of SAV1 and Dendrin
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