2i0l

From Proteopedia

(Difference between revisions)

Revision as of 10:23, 12 January 2022

X-ray crystal structure of Sap97 PDZ2 bound to the C-terminal peptide of HPV18 E6.

Structural highlights

2i0l is a 4 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] [VE6_HPV18] Transcriptional transactivator. Binds double stranded DNA (By similarity). Has transforming activity. Inactivates, with E6-AP ubiquitin-protein ligase, the human p53/TP53 tumor suppressor protein by targeting it to degradation. Binds and targets human MUPP1/MPDZ protein to degradation. Those two functions presumably contribute to transforming activity. Interaction with human FBLN1 protein also seems to be linked to cell transformation.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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.

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Leonoudakis D, Conti LR, Radeke CM, McGuire LM, Vandenberg CA. A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. J Biol Chem. 2004 Apr 30;279(18):19051-63. Epub 2004 Feb 11. PMID:14960569 doi:http://dx.doi.org/10.1074/jbc.M400284200
↑ Mauceri D, Cattabeni F, Di Luca M, Gardoni F. Calcium/calmodulin-dependent protein kinase II phosphorylation drives synapse-associated protein 97 into spines. J Biol Chem. 2004 May 28;279(22):23813-21. Epub 2004 Mar 24. PMID:15044483 doi:http://dx.doi.org/10.1074/jbc.M402796200
↑ Nakagawa T, Futai K, Lashuel HA, Lo I, Okamoto K, Walz T, Hayashi Y, Sheng M. Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions. Neuron. 2004 Oct 28;44(3):453-67. PMID:15504326 doi:http://dx.doi.org/10.1016/j.neuron.2004.10.012
↑ 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
↑ Zhang Y, Dasgupta J, Ma RZ, Banks L, Thomas M, Chen XS. Structures of a human papillomavirus (HPV) E6 polypeptide bound to MAGUK proteins: mechanisms of targeting tumor suppressors by a high-risk HPV oncoprotein. J Virol. 2007 Apr;81(7):3618-26. Epub 2007 Jan 31. PMID:17267502 doi:10.1128/JVI.02044-06

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2i0l"

@@ Line 3: / Line 3: @@
 <StructureSection load='2i0l' size='340' side='right'caption='[[2i0l]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2i0l]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. 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 [http://proteopedia.org/fgij/fg.htm?mol=2I0L FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2i0l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. 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'>[http://proteopedia.org/fgij/fg.htm?mol=2i0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i0l OCA], [http://pdbe.org/2i0l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i0l RCSB], [http://www.ebi.ac.uk/pdbsum/2i0l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2i0l ProSAT]</span></td></tr>
+</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>
 == Function ==
-[[http://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>  [[http://www.uniprot.org/uniprot/VE6_HPV18 VE6_HPV18]] Transcriptional transactivator. Binds double stranded DNA (By similarity). Has transforming activity. Inactivates, with E6-AP ubiquitin-protein ligase, the human p53/TP53 tumor suppressor protein by targeting it to degradation. Binds and targets human MUPP1/MPDZ protein to degradation. Those two functions presumably contribute to transforming activity. Interaction with human FBLN1 protein also seems to be linked to cell transformation.
+[[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>  [[https://www.uniprot.org/uniprot/VE6_HPV18 VE6_HPV18]] Transcriptional transactivator. Binds double stranded DNA (By similarity). Has transforming activity. Inactivates, with E6-AP ubiquitin-protein ligase, the human p53/TP53 tumor suppressor protein by targeting it to degradation. Binds and targets human MUPP1/MPDZ protein to degradation. Those two functions presumably contribute to transforming activity. Interaction with human FBLN1 protein also seems to be linked to cell transformation.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

2i0l

From Proteopedia

Revision as of 10:23, 12 January 2022

X-ray crystal structure of Sap97 PDZ2 bound to the C-terminal peptide of HPV18 E6.

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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