2i0i

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[[Image:2i0i.jpg|left|200px]]
 
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==X-ray crystal structure of Sap97 PDZ3 bound to the C-terminal peptide of HPV18 E6==
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The line below this paragraph, containing "STRUCTURE_2i0i", creates the "Structure Box" on the page.
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<StructureSection load='2i0i' size='340' side='right'caption='[[2i0i]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2i0i]] is a 6 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=2I0I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I0I FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2i0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i0i OCA], [https://pdbe.org/2i0i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i0i RCSB], [https://www.ebi.ac.uk/pdbsum/2i0i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i0i ProSAT]</span></td></tr>
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{{STRUCTURE_2i0i| PDB=2i0i | SCENE= }}
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</table>
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== Function ==
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'''X-ray crystal structure of Sap97 PDZ3 bound to the C-terminal peptide of HPV18 E6'''
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==Overview==
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Check<jmol>
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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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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i0/2i0i_consurf.spt"</scriptWhenChecked>
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==About this Structure==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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2I0I is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I0I OCA].
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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==Reference==
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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=2i0i ConSurf].
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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:[http://www.ncbi.nlm.nih.gov/pubmed/17267502 17267502]
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Human papillomavirus type 18]]
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[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Single protein]]
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[[Category: Banks L]]
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[[Category: Banks, L.]]
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[[Category: Chen XS]]
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[[Category: Chen, X S.]]
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[[Category: Dasgupta J]]
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[[Category: Dasgupta, J.]]
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[[Category: Thomas M]]
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[[Category: Thomas, M.]]
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[[Category: Zhang Y]]
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[[Category: Zhang, Y.]]
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[[Category: Cervical carcinoma]]
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[[Category: Hpv18 e6]]
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[[Category: Sap97 pdz3]]
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[[Category: Tumor suppressor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:55:52 2008''
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Current revision

X-ray crystal structure of Sap97 PDZ3 bound to the C-terminal peptide of HPV18 E6

PDB ID 2i0i

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