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==Crystal Structure of PALS1/Crb complex==
==Crystal Structure of PALS1/Crb complex==
<StructureSection load='4wsi' size='340' side='right' caption='[[4wsi]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
<StructureSection load='4wsi' size='340' side='right'caption='[[4wsi]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4wsi]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WSI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WSI FirstGlance]. <br>
<table><tr><td colspan='2'>[[4wsi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WSI FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4wsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wsi OCA], [http://pdbe.org/4wsi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wsi RCSB], [http://www.ebi.ac.uk/pdbsum/4wsi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wsi 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]] 2.95&#8491;</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=4wsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wsi OCA], [https://pdbe.org/4wsi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wsi RCSB], [https://www.ebi.ac.uk/pdbsum/4wsi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wsi ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/MPP5_HUMAN MPP5_HUMAN]] May play a role in tight junctions biogenesis and in the establishment of cell polarity in epithelial cells. May modulate SC6A1/GAT1-mediated GABA uptake by stabilizing the transporter. Required for localization of EZR to the apical membrane of parietal cells and may play a role in the dynamic remodeling of the apical cytoskeleton (By similarity). [[http://www.uniprot.org/uniprot/CRB_DROME CRB_DROME]] Plays a central role in cell polarity establishment. Participates in the assembly, positioning and maintenance of adherens junctions via its interaction with the SAC complex. Controls the coalescence of the spots of zonula adherens (ZA) into a adhesive ring around the cells. It may act as a signal. Involved in morphogenesis of the photoreceptor rhabdomere, for positioning and growth of rhabdomere and AJ during the crucial period of photoreceptor extension along the proximodistal axis of the retina.<ref>PMID:2344615</ref
[https://www.uniprot.org/uniprot/CRB_DROME CRB_DROME] Plays a central role in cell polarity establishment. Participates in the assembly, positioning and maintenance of adherens junctions via its interaction with the SAC complex. Controls the coalescence of the spots of zonula adherens (ZA) into a adhesive ring around the cells. It may act as a signal. Involved in morphogenesis of the photoreceptor rhabdomere, for positioning and growth of rhabdomere and AJ during the crucial period of photoreceptor extension along the proximodistal axis of the retina.<ref>PMID:2344615</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Crumbs (Crb) complex, formed by Crb, PALS1, and PATJ, is evolutionarily conserved in metazoans and acts as a master cell-growth and -polarity regulator at the apical membranes in polarized epithelia. Crb intracellular functions, including its direct binding to PALS1, are mediated by Crb's highly conserved 37-residue cytoplasmic tail. However, the mechanistic basis governing the highly specific Crb-PALS1 complex formation is unclear, as reported interaction between the Crb tail (Crb-CT) and PALS1 PSD-95/DLG/ZO-1 (PDZ) domain is weak and promiscuous. Here we have discovered that the PDZ-Src homolgy 3 (SH3)-Guanylate kinase (GK) tandem of PALS1 binds to Crb-CT with a dissociation constant of 70 nM, which is approximately 100-fold stronger than the PALS1 PDZ-Crb-CT interaction. The crystal structure of the PALS1 PDZ-SH3-GK-Crb-CT complex reveals that PDZ-SH3-GK forms a structural supramodule with all three domains contributing to the tight binding to Crb. Mutations disrupting the tertiary interactions of the PDZ-SH3-GK supramodule weaken the PALS1-Crb interaction and compromise PALS1-mediated polarity establishment in Madin-Darby canine kidney (MDCK) cysts. We further show that specific target binding of other members of membrane-associated guanylate kinases (MAGUKs) (e.g., CASK binding to neurexin) also requires the presence of their PDZ-SH3-GK tandems.
 
Structure of Crumbs tail in complex with the PALS1 PDZ-SH3-GK tandem reveals a highly specific assembly mechanism for the apical Crumbs complex.,Li Y, Wei Z, Yan Y, Wan Q, Du Q, Zhang M Proc Natl Acad Sci U S A. 2014 Nov 10. pii: 201416515. PMID:25385611<ref>PMID:25385611</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4wsi" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Li, Y]]
[[Category: Drosophila melanogaster]]
[[Category: Wei, Z]]
[[Category: Homo sapiens]]
[[Category: Zhang, M]]
[[Category: Large Structures]]
[[Category: Peptide binding protein]]
[[Category: Li Y]]
[[Category: Supramodule]]
[[Category: Wei Z]]
[[Category: Zhang M]]

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