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| | <StructureSection load='6twu' size='340' side='right'caption='[[6twu]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='6twu' size='340' side='right'caption='[[6twu]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6twu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TWU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TWU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6twu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_papillomavirus_type_16 Human papillomavirus type 16]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TWU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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]] 2.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANXA2, ANX2, ANX2L4, CAL1H, LPC2D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6twu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6twu OCA], [http://pdbe.org/6twu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6twu RCSB], [http://www.ebi.ac.uk/pdbsum/6twu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6twu ProSAT]</span></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=6twu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6twu OCA], [https://pdbe.org/6twu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6twu RCSB], [https://www.ebi.ac.uk/pdbsum/6twu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6twu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MAGI1_HUMAN MAGI1_HUMAN]] May play a role as scaffolding protein at cell-cell junctions. May regulate acid-induced ASIC3 currents by modulating its expression at the cell surface (By similarity). [[http://www.uniprot.org/uniprot/VE6_HPV16 VE6_HPV16]] Plays a major role in the induction and maintenance of cellular transformation. Acts mainly as an oncoprotein by stimulating the destruction of many host cell key regulatory proteins. E6 associates with host E6-AP ubiquitin-protein ligase, and inactivates tumor suppressors TP53 and TP73 by targeting them to the 26S proteasome for degradation. In turn, DNA damage and chromosomal instabilities increase and lead to cell proliferation and cancer development. The complex E6/E6P targets several other substrates to degradation via the proteasome including host NFX1-91, a repressor of human telomerase reverse transcriptase (hTERT). The resulting increased expression of hTERT prevents the shortening of telomere length leading to cell immortalization. Other cellular targets including Bak, Fas-associated death domain-containing protein (FADD) and procaspase 8, are degraded by E6/E6AP causing inhibition of apoptosis. E6 also inhibits immune response by interacting with host IRF3 and TYK2. These interactions prevent IRF3 transcriptional activities and inhibit TYK2-mediated JAK-STAT activation by interferon alpha resulting in inhibition of the interferon signaling pathway.<ref>PMID:8598912</ref> <ref>PMID:9649509</ref> <ref>PMID:10523853</ref> | + | [https://www.uniprot.org/uniprot/MAGI1_HUMAN MAGI1_HUMAN] May play a role as scaffolding protein at cell-cell junctions. May regulate acid-induced ASIC3 currents by modulating its expression at the cell surface (By similarity).[https://www.uniprot.org/uniprot/ANXA2_HUMAN ANXA2_HUMAN] Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6twu" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6twu" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Guanylate kinase 3D structures|Guanylate kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | + | [[Category: Human papillomavirus type 16]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cousido-Siah, A]] | + | [[Category: Cousido-Siah A]] |
| - | [[Category: Gogl, G]] | + | [[Category: Gogl G]] |
| - | [[Category: Trave, G]] | + | [[Category: Trave G]] |
| - | [[Category: Motif]]
| + | |
| - | [[Category: Pdz domain]]
| + | |
| - | [[Category: Peptide binding protein]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| Structural highlights
Function
MAGI1_HUMAN May play a role as scaffolding protein at cell-cell junctions. May regulate acid-induced ASIC3 currents by modulating its expression at the cell surface (By similarity).ANXA2_HUMAN Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response.
Publication Abstract from PubMed
Protein-protein interaction motifs are often alterable by post-translational modifications. For example, 19% of predicted human PDZ domain-binding motifs (PBMs) have been experimentally proven to be phosphorylated, and up to 82% are theoretically phosphorylatable. Phosphorylation of PBMs may drastically rewire their interactomes, by altering their affinities for PDZ domains and 14-3-3 proteins. The effect of phosphorylation is often analyzed by performing "phosphomimetic" mutations. Here, we focused on the PBMs of HPV16-E6 viral oncoprotein and human RSK1 kinase. We measured the binding affinities of native, phosphorylated, and phosphomimetic variants of both PBMs toward the 266 human PDZ domains. We co-crystallized all the motif variants with a selected PDZ domain to characterize the structural consequence of the different modifications. Finally, we elucidated the structural basis of PBM capture by 14-3-3 proteins. This study provides novel atomic and interactomic insights into phosphorylatable dual specificity motifs and the differential effects of phosphorylation and phosphomimetic approaches.
Dual Specificity PDZ- and 14-3-3-Binding Motifs: A Structural and Interactomics Study.,Gogl G, Jane P, Caillet-Saguy C, Kostmann C, Bich G, Cousido-Siah A, Nyitray L, Vincentelli R, Wolff N, Nomine Y, Sluchanko NN, Trave G Structure. 2020 Apr 6. pii: S0969-2126(20)30092-7. doi:, 10.1016/j.str.2020.03.010. PMID:32294469[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gogl G, Jane P, Caillet-Saguy C, Kostmann C, Bich G, Cousido-Siah A, Nyitray L, Vincentelli R, Wolff N, Nomine Y, Sluchanko NN, Trave G. Dual Specificity PDZ- and 14-3-3-Binding Motifs: A Structural and Interactomics Study. Structure. 2020 Apr 6. pii: S0969-2126(20)30092-7. doi:, 10.1016/j.str.2020.03.010. PMID:32294469 doi:http://dx.doi.org/10.1016/j.str.2020.03.010
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