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| | ==Solution structure of a complex consisting of hDlg/SAP-97 residues 318-406 and HPV51 oncoprotein E6 residues 141-151== | | ==Solution structure of a complex consisting of hDlg/SAP-97 residues 318-406 and HPV51 oncoprotein E6 residues 141-151== |
| - | <StructureSection load='2m3m' size='340' side='right' caption='[[2m3m]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2m3m' size='340' side='right'caption='[[2m3m]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m3m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_papillomavirus_type_51 Human papillomavirus type 51]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M3M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M3M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m3m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_papillomavirus_51 Human papillomavirus 51]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M3M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M3M FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m3l|2m3l]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DLG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), E6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10595 Human papillomavirus type 51])</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=2m3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m3m OCA], [https://pdbe.org/2m3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m3m RCSB], [https://www.ebi.ac.uk/pdbsum/2m3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m3m ProSAT]</span></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=2m3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m3m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2m3m RCSB], [http://www.ebi.ac.uk/pdbsum/2m3m PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DLG1_HUMAN DLG1_HUMAN]] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.<ref>PMID:10656683</ref> <ref>PMID:12445884</ref> <ref>PMID:14699157</ref> <ref>PMID:15263016</ref> <ref>PMID:19213956</ref> <ref>PMID:20605917</ref> [[http://www.uniprot.org/uniprot/VE6_HPV51 VE6_HPV51]] Transcriptional transactivator. Binds double stranded DNA (By similarity). | + | [https://www.uniprot.org/uniprot/DLG1_HUMAN DLG1_HUMAN] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.<ref>PMID:10656683</ref> <ref>PMID:12445884</ref> <ref>PMID:14699157</ref> <ref>PMID:15263016</ref> <ref>PMID:19213956</ref> <ref>PMID:20605917</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2m3m" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Human papillomavirus type 51]] | + | [[Category: Human papillomavirus 51]] |
| - | [[Category: Gorlach, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Mischo, A]] | + | [[Category: Gorlach M]] |
| - | [[Category: Ohlenschlager, O]] | + | [[Category: Mischo A]] |
| - | [[Category: Dlg]] | + | [[Category: Ohlenschlager O]] |
| - | [[Category: E6]]
| + | |
| - | [[Category: Hdlg]]
| + | |
| - | [[Category: Hdlg1]]
| + | |
| - | [[Category: Hdlgpdz2]]
| + | |
| - | [[Category: Hpv]]
| + | |
| - | [[Category: Oncogene protein]]
| + | |
| - | [[Category: Oncoprotein - cell adhesion protein complex]]
| + | |
| - | [[Category: Oncoprotein e6]]
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| - | [[Category: Oncoprotein-cell adhesion complex]]
| + | |
| - | [[Category: Papillomavirus e6 protein]]
| + | |
| - | [[Category: Pdz domain]]
| + | |
| - | [[Category: Sap-97]]
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| - | [[Category: Viral]]
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| Structural highlights
Function
DLG1_HUMAN Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
The high-risk human papilloma virus (HPV) oncoproteins E6 and E7 interact with key cellular regulators and are etiological agents for tumorigenesis and tumor maintenance in cervical cancer and other malignant conditions. E6 induces degradation of the tumor suppressor p53, activates telomerase and deregulates cell polarity. Analysis of E6 derived from a number of high risk HPV finally yielded the first structure of a wild-type HPV E6 domain (PDB 2M3L) representing the second zinc-binding domain of HPV 51 E6 (termed 51Z2) determined by NMR spectroscopy. The 51Z2 structure provides clues about HPV-type specific structural differences between E6 proteins. The observed temperature sensitivity of the well-folded wild-type E6 domain implies a significant malleability of the oncoprotein in vivo. Hence, the structural differences between individual E6 and their malleability appear, together with HPV type-specific surface exposed side-chains, to provide the structural basis for the different interaction networks reported for individual E6 proteins. Furthermore, the interaction of 51Z2 with a PDZ domain of hDlg was analyzed. Human Dlg constitutes a prototypic representative of the large family of PDZ proteins regulating cell polarity, which are common targets of high-risk HPV E6. Nine C-terminal residues of 51Z2 interact with the second PDZ domain of hDlg2. Surface plasmon resonance in conjunction with the NMR spectroscopy derived complex structure (PDB 2M3M) indicate that E6 residues N-terminal to the canonical PDZ-BM of E6 significantly contribute to this interaction and increase affinity. The structure of the complex reveals how residues outside of the classical PDZ-BM enhance the affinity of E6 towards PDZ domains. Such mechanism facilitates successful competition of E6 with cellular PDZ-binding proteins and may apply to PDZ-binding proteins of other viruses as well.
Structural insights into a wildtype domain of the oncoprotein E6 and its interaction with a PDZ domain.,Mischo A, Ohlenschlager O, Hortschansky P, Ramachandran R, Gorlach M PLoS One. 2013 Apr 30;8(4):e62584. doi: 10.1371/journal.pone.0062584. Print 2013. PMID:23638119[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ishidate T, Matsumine A, Toyoshima K, Akiyama T. The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase. Oncogene. 2000 Jan 20;19(3):365-72. PMID:10656683 doi:10.1038/sj.onc.1203309
- ↑ Godreau D, Vranckx R, Maguy A, Rucker-Martin C, Goyenvalle C, Abdelshafy S, Tessier S, Couetil JP, Hatem SN. Expression, regulation and role of the MAGUK protein SAP-97 in human atrial myocardium. Cardiovasc Res. 2002 Dec;56(3):433-42. PMID:12445884
- ↑ Laprise P, Viel A, Rivard N. Human homolog of disc-large is required for adherens junction assembly and differentiation of human intestinal epithelial cells. J Biol Chem. 2004 Mar 12;279(11):10157-66. Epub 2003 Dec 29. PMID:14699157 doi:10.1074/jbc.M309843200
- ↑ Xavier R, Rabizadeh S, Ishiguro K, Andre N, Ortiz JB, Wachtel H, Morris DG, Lopez-Ilasaca M, Shaw AC, Swat W, Seed B. Discs large (Dlg1) complexes in lymphocyte activation. J Cell Biol. 2004 Jul 19;166(2):173-8. PMID:15263016 doi:10.1083/jcb.200309044
- ↑ El-Haou S, Balse E, Neyroud N, Dilanian G, Gavillet B, Abriel H, Coulombe A, Jeromin A, Hatem SN. Kv4 potassium channels form a tripartite complex with the anchoring protein SAP97 and CaMKII in cardiac myocytes. Circ Res. 2009 Mar 27;104(6):758-69. doi: 10.1161/CIRCRESAHA.108.191007. Epub, 2009 Feb 12. PMID:19213956 doi:10.1161/CIRCRESAHA.108.191007
- ↑ Sabio G, Cerezo-Guisado MI, Del Reino P, Inesta-Vaquera FA, Rousseau S, Arthur JS, Campbell DG, Centeno F, Cuenda A. p38gamma regulates interaction of nuclear PSF and RNA with the tumour-suppressor hDlg in response to osmotic shock. J Cell Sci. 2010 Aug 1;123(Pt 15):2596-604. doi: 10.1242/jcs.066514. Epub 2010, Jul 6. PMID:20605917 doi:10.1242/jcs.066514
- ↑ Mischo A, Ohlenschlager O, Hortschansky P, Ramachandran R, Gorlach M. Structural insights into a wildtype domain of the oncoprotein E6 and its interaction with a PDZ domain. PLoS One. 2013 Apr 30;8(4):e62584. doi: 10.1371/journal.pone.0062584. Print 2013. PMID:23638119 doi:10.1371/journal.pone.0062584
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