View source for 7qcr


==MLLT4/Afadin PDZ domain in complex with the C-terminal peptide from protein E of SARS-CoV-2==
<StructureSection load='7qcr' size='340' side='right'caption='[[7qcr]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qcr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QCR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QCR 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]] 2.28&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7qcr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qcr OCA], [https://pdbe.org/7qcr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qcr RCSB], [https://www.ebi.ac.uk/pdbsum/7qcr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qcr ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/AFAD_HUMAN AFAD_HUMAN] Note=A chromosomal aberration involving MLLT4 is associated with acute leukemias. Translocation t(6;11)(q27;q23) with MLL/HRX. The result is a rogue activator protein.
== Function ==
[https://www.uniprot.org/uniprot/AFAD_HUMAN AFAD_HUMAN] Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton.
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== Publication Abstract from PubMed ==
The C-terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein E contains a PBM (PDZ-binding motif) targeting PDZ (PSD-95/Dlg/ZO-1) domains, which is identical to the PBM of SARS-CoV. The latter is involved in the pathogenicity of the virus. Recently, we identified 10 human PDZ-containing proteins showing significant interactions with SARS-CoV-2 protein E PBM. We selected several of them involved in cellular junctions and cell polarity (TJP1, PARD3, MLLT4, and LNX2) and MPP5/PALS1 previously shown to interact with SARS-CoV E PBM. Targeting cellular junctions and polarity components is a common strategy by viruses to hijack cell machinery to their advantage. In this study, we showed that these host PDZ domains TJP1, PARD3, MLLT4, LNX2, and MPP5/PALS1 interact in a PBM-dependent manner in vitro and colocalize with the full-length E protein in cellulo, sequestrating the PDZ domains to the Golgi compartment. We solved three crystal structures of complexes between human LNX2, MLLT4, and MPP5 PDZs and SARS-CoV-2 E PBM highlighting its binding preferences for several cellular targets. Finally, we showed different affinities for the PDZ domains with the original SARS-CoV-2 C-terminal sequence containing the PBM and the one of the beta variant that contains a mutation close to the PBM. The acquired mutations in the E protein localized near the PBM might have important effects both on the structure and the ion-channel activity of the E protein and on the host machinery targeted by the variants during the infection.

Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins.,Zhu Y, Alvarez F, Wolff N, Mechaly A, Brule S, Neitthoffer B, Etienne-Manneville S, Haouz A, Boeda B, Caillet-Saguy C Front Microbiol. 2022 Feb 23;13:829094. doi: 10.3389/fmicb.2022.829094. , eCollection 2022. PMID:35283834<ref>PMID:35283834</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 7qcr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Alvarez F]]
[[Category: Caillet-Saguy C]]
[[Category: Haouz A]]
[[Category: Mechaly A]]
[[Category: Zhu Y]]