2i0l
From Proteopedia
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<StructureSection load='2i0l' size='340' side='right'caption='[[2i0l]], [[Resolution|resolution]] 2.31Å' scene=''> | <StructureSection load='2i0l' size='340' side='right'caption='[[2i0l]], [[Resolution|resolution]] 2.31Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2i0l]] is a 4 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2i0l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_papillomavirus_type_18 Human papillomavirus type 18] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I0L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I0L FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31Å</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=2i0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i0l OCA], [https://pdbe.org/2i0l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i0l RCSB], [https://www.ebi.ac.uk/pdbsum/2i0l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i0l ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/DLG1_RAT DLG1_RAT] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel (By similarity). May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation.<ref>PMID:14960569</ref> <ref>PMID:15044483</ref> <ref>PMID:15504326</ref> <ref>PMID:19213956</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2i0l ConSurf]. | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2i0l ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Human papillomavirus (HPV) E6 oncoprotein targets certain tumor suppressors such as MAGI-1 and SAP97/hDlg for degradation. A short peptide at the C terminus of E6 interacts specifically with the PDZ domains of these tumor suppressors, which is a property unique to high-risk HPVs that are associated with cervical cancer. The detailed recognition mechanisms between HPV E6 and PDZ proteins are unclear. To understand the specific binding of cellular PDZ substrates by HPV E6, we have solved the crystal structures of the complexes containing a peptide from HPV18 E6 bound to three PDZ domains from MAGI-1 and SAP97/Dlg. The complex crystal structures reveal novel features of PDZ peptide recognition that explain why high-risk HPV E6 can specifically target these cellular tumor suppressors for destruction. Moreover, a new peptide-binding loop on these PDZs is identified as interacting with the E6 peptide. Furthermore, we have identified an arginine residue, unique to high-risk HPV E6 but outside the canonical core PDZ recognition motif, that plays an important role in the binding of the PDZs of both MAGI-I and SAP97/Dlg, the mutation of which abolishes E6's ability to degrade the two proteins. Finally, we have identified a dimer form of MAGI-1 PDZ domain 1 in the cocrystal structure with E6 peptide, which may have functional relevance for MAGI-1 activity. In addition to its novel insights into the biochemistry of PDZ interactions, this study is important for understanding HPV-induced oncogenesis; this could provide a basis for developing antiviral and anticancer compounds. | ||
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| - | Structures of a human papillomavirus (HPV) E6 polypeptide bound to MAGUK proteins: mechanisms of targeting tumor suppressors by a high-risk HPV oncoprotein.,Zhang Y, Dasgupta J, Ma RZ, Banks L, Thomas M, Chen XS J Virol. 2007 Apr;81(7):3618-26. Epub 2007 Jan 31. PMID:17267502<ref>PMID:17267502</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 2i0l" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Human papillomavirus type 18]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Banks | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Chen | + | [[Category: Banks L]] |
| - | [[Category: Dasgupta | + | [[Category: Chen XS]] |
| - | [[Category: Thomas | + | [[Category: Dasgupta J]] |
| - | [[Category: Zhang | + | [[Category: Thomas M]] |
| - | + | [[Category: Zhang Y]] | |
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Current revision
X-ray crystal structure of Sap97 PDZ2 bound to the C-terminal peptide of HPV18 E6.
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