6xa6
From Proteopedia
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| - | ==== | + | ==Crystal Structure of Human Scribble PDZ3:Vangl2 Complex== |
| - | <StructureSection load='6xa6' size='340' side='right'caption='[[6xa6]]' scene=''> | + | <StructureSection load='6xa6' size='340' side='right'caption='[[6xa6]], [[Resolution|resolution]] 1.95Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6xa6]] 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=6XA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XA6 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=6xa6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xa6 OCA], [https://pdbe.org/6xa6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xa6 RCSB], [https://www.ebi.ac.uk/pdbsum/6xa6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xa6 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]] 1.95Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6xa6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xa6 OCA], [https://pdbe.org/6xa6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xa6 RCSB], [https://www.ebi.ac.uk/pdbsum/6xa6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xa6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/SCRIB_HUMAN SCRIB_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SCRIB_HUMAN SCRIB_HUMAN] Scaffold protein involved in different aspects of polarized cells differentiation regulating epithelial and neuronal morphogenesis. Most probably functions in the establishment of apico-basal cell polarity. May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium. May also function in cell migration and adhesion and hence regulate cell invasion through MAPK signaling. May play a role in exocytosis and in the targeting synaptic vesicles to synapses. Functions as an activator of Rac GTPase activity.<ref>PMID:15182672</ref> <ref>PMID:15775968</ref> <ref>PMID:16344308</ref> <ref>PMID:16965391</ref> <ref>PMID:18641685</ref> <ref>PMID:18716323</ref> <ref>PMID:19041750</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Scribble is a critical cell polarity regulator that has been shown to work as either an oncogene or tumor suppressor in a context dependent manner, and also impacts cell migration, tissue architecture and immunity. Mutations in Scribble lead to neural tube defects in mice and humans, which has been attributed to a loss of interaction with the planar cell polarity regulator Vangl2. We show that the Scribble PDZ domains 1, 2 and 3 are able to interact with the C-terminal PDZ binding motif of Vangl2 and have now determined crystal structures of these Scribble PDZ domains bound to the Vangl2 peptide. Mapping of mammalian neural tube defect mutations reveal that mutations located distal to the canonical PDZ domain ligand binding groove can not only ablate binding to Vangl2 but also disrupt binding to multiple other signaling regulators. Our findings suggest that PDZ-associated neural tube defect mutations in Scribble may not simply act in a Vangl2 dependent manner but as broad-spectrum loss of function mutants by disrupting the global Scribble-mediated interaction network. | ||
| + | |||
| + | Structural basis of the human Scribble-Vangl2 association in health and disease.,How JY, Stephens R, Lim KYB, Humbert PO, Kvansakul M Biochem J. 2021 Mar 8. pii: 228041. doi: 10.1042/BCJ20200816. PMID:33684218<ref>PMID:33684218</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6xa6" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: How JY]] |
| + | [[Category: Kvansakul M]] | ||
Current revision
Crystal Structure of Human Scribble PDZ3:Vangl2 Complex
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