1n25
From Proteopedia
(Difference between revisions)
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<StructureSection load='1n25' size='340' side='right'caption='[[1n25]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='1n25' size='340' side='right'caption='[[1n25]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1n25]] is a 2 chain structure. The November 2003 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Simian Virus 40'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2003_11 10.2210/rcsb_pdb/mom_2003_11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N25 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1n25]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta_polyomavirus_1 Macaca mulatta polyomavirus 1]. The November 2003 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Simian Virus 40'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2003_11 10.2210/rcsb_pdb/mom_2003_11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N25 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.8Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=1n25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n25 OCA], [https://pdbe.org/1n25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n25 RCSB], [https://www.ebi.ac.uk/pdbsum/1n25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n25 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=1n25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n25 OCA], [https://pdbe.org/1n25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n25 RCSB], [https://www.ebi.ac.uk/pdbsum/1n25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n25 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/LT_SV40 LT_SV40] Isoform large T antigen is a key early protein essential for both driving viral replication and inducing cellular transformation. Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle and by autoregulating the synthesis of viral early mRNA. Displays highly oncogenic activities by corrupting the host cellular checkpoint mechanisms that guard cell division and the transcription, replication, and repair of DNA. Participates in the modulation of cellular gene expression preceeding viral DNA replication. This step involves binding to host key cell cycle regulators retinoblastoma protein RB1/pRb and TP53. Induces the disassembly of host E2F1 transcription factors from RB1, thus promoting transcriptional activation of E2F1-regulated S-phase genes. Inhibits host TP53 binding to DNA, abrogating the ability of TP53 to stimulate gene expression. Plays the role of a TFIID-associated factor (TAF) in transcription initiation for all three RNA polymerases, by stabilizing the TBP-TFIIA complex on promoters. Initiates viral DNA replication and unwinding via interactions with the viral origin of replication. Binds two adjacent sites in the SV40 origin. The replication fork movement is facilitated by Large T antigen helicase activity. Activates the transcription of viral late mRNA, through host TBP and TFIIA stabilization. Interferes with histone deacetylation mediated by HDAC1, leading to activation of transcription. May inactivate the growth-suppressing properties of the E3 ubiquitin ligase CUL7.<ref>PMID:8647434</ref> <ref>PMID:9632777</ref> <ref>PMID:9488456</ref> <ref>PMID:15680424</ref> <ref>PMID:15611062</ref> <ref>PMID:17341466</ref> <ref>PMID:18922873</ref> Isoform 17kT antigen targets host RBL2 for degradation and promotes cell proliferation. Transactivates host cyclin A promoter through its J domain.<ref>PMID:8647434</ref> <ref>PMID:9632777</ref> <ref>PMID:9488456</ref> <ref>PMID:15680424</ref> <ref>PMID:15611062</ref> <ref>PMID:17341466</ref> <ref>PMID:18922873</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=1n25 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=1n25 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | The oncoprotein large tumour antigen (LTag) is encoded by the DNA tumour virus simian virus 40. LTag transforms cells and induces tumours in animals by altering the functions of tumour suppressors (including pRB and p53) and other key cellular proteins. LTag is also a molecular machine that distorts/melts the replication origin of the viral genome and unwinds duplex DNA. LTag therefore seems to be a functional homologue of the eukaryotic minichromosome maintenance (MCM) complex. Here we present the X-ray structure of a hexameric LTag with DNA helicase activity. The structure identifies the p53-binding surface and reveals the structural basis of hexamerization. The hexamer contains a long, positively charged channel with an unusually large central chamber that binds both single-stranded and double-stranded DNA. The hexamer organizes into two tiers that can potentially rotate relative to each other through connecting alpha-helices to expand/constrict the channel, producing an 'iris' effect that could be used for distorting or melting the origin and unwinding DNA at the replication fork. | ||
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| - | Structure of the replicative helicase of the oncoprotein SV40 large tumour antigen.,Li D, Zhao R, Lilyestrom W, Gai D, Zhang R, DeCaprio JA, Fanning E, Jochimiak A, Szakonyi G, Chen XS Nature. 2003 May 29;423(6939):512-8. PMID:12774115<ref>PMID:12774115</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1n25" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Macaca mulatta polyomavirus 1]] | ||
[[Category: RCSB PDB Molecule of the Month]] | [[Category: RCSB PDB Molecule of the Month]] | ||
[[Category: Simian Virus 40]] | [[Category: Simian Virus 40]] | ||
| - | [[Category: Chen | + | [[Category: Chen XS]] |
| - | [[Category: DeCaprio | + | [[Category: DeCaprio JA]] |
| - | [[Category: Fanning | + | [[Category: Fanning E]] |
| - | [[Category: Gai | + | [[Category: Gai D]] |
| - | [[Category: Jochimiak | + | [[Category: Jochimiak A]] |
| - | [[Category: Li | + | [[Category: Li D]] |
| - | [[Category: Lilyestrom | + | [[Category: Lilyestrom W]] |
| - | [[Category: Szakonyi | + | [[Category: Szakonyi G]] |
| - | [[Category: Zhang | + | [[Category: Zhang R]] |
| - | [[Category: Zhao | + | [[Category: Zhao R]] |
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Current revision
Crystal structure of the SV40 Large T antigen helicase domain
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