View source for 7qtp


==Structural biology of the NS1 avian influenza protein subversion on the Scribble cell polarity module==
<StructureSection load='7qtp' size='340' side='right'caption='[[7qtp]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qtp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/H5N1_subtype H5N1 subtype] 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=7QTP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QTP 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]] 1.9&#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=7qtp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qtp OCA], [https://pdbe.org/7qtp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qtp RCSB], [https://www.ebi.ac.uk/pdbsum/7qtp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qtp ProSAT]</span></td></tr>
</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 highly conserved regulator of cell polarity, a process that enables the generation of asymmetry at the cellular and tissue level in higher organisms. Scribble acts in concert with Disc-large (Dlg) and Lethal-2-giant larvae (Lgl) to form the Scribble polarity complex, and its functional dysregulation is associated with poor prognosis during viral infections. Viruses have been shown to interfere with Scribble by targeting Scribble PDZ domains to subvert the network of interactions that enable normal control of cell polarity via Scribble, as well as the localisation of the Scribble module within the cell. The influenza A virus NS1 protein was shown to bind to human Scribble (SCRIB) via its C-terminal PDZ binding motif (PBM). It was reported that the PBM sequence ESEV is a virulence determinant for influenza A virus H5N1 whilst other sequences, such as ESKV, KSEV and RSKV, demonstrated no affinity towards Scribble. We now show, using isothermal titration calorimetry (ITC), that ESKV and KSEV bind to SCRIB PDZ domains and that ESEV unexpectedly displayed an affinity towards all four PDZs and not just a selected few. We then define the structural basis for the interactions of SCRIB PDZ1 domain with ESEV and ESKV PBM motifs, as well as SCRIB PDZ3 with the ESKV PBM motif. These findings will serve as a platform for understanding the role of Scribble PDZ domains and their interactions with different NS1 PBMs and the mechanisms that mediate cell polarity within the context of the pathogenesis of influenza A virus.

Structural Basis of the Avian Influenza NS1 Protein Interactions with the Cell Polarity Regulator Scribble.,Javorsky A, Humbert PO, Kvansakul M Viruses. 2022 Mar 11;14(3):583. doi: 10.3390/v14030583. PMID:35336989<ref>PMID:35336989</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7qtp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: H5N1 subtype]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Humbert PO]]
[[Category: Javorsky A]]
[[Category: Kvansakul M]]