1ejl

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[[Image:1ejl.gif|left|200px]]
 
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{{Structure
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==MOUSE IMPORTIN ALPHA-SV40 LARGE T ANTIGEN NLS PEPTIDE COMPLEX==
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|PDB= 1ejl |SIZE=350|CAPTION= <scene name='initialview01'>1ejl</scene>, resolution 2.80&Aring;
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<StructureSection load='1ejl' size='340' side='right'caption='[[1ejl]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<table><tr><td colspan='2'>[[1ejl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta_polyomavirus_1 Macaca mulatta polyomavirus 1] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EJL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EJL FirstGlance]. <br>
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|ACTIVITY=
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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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|GENE=
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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=1ejl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ejl OCA], [https://pdbe.org/1ejl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ejl RCSB], [https://www.ebi.ac.uk/pdbsum/1ejl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ejl ProSAT]</span></td></tr>
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}}
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ej/1ejl_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1ejl ConSurf].
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<div style="clear:both"></div>
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'''MOUSE IMPORTIN ALPHA-SV40 LARGE T ANTIGEN NLS PEPTIDE COMPLEX'''
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==See Also==
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*[[Importin 3D structures|Importin 3D structures]]
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*[[Large T Antigen|Large T Antigen]]
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==Overview==
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== References ==
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Importin-alpha is the nuclear import receptor that recognizes cargo proteins which contain classical monopartite and bipartite nuclear localization sequences (NLSs), and facilitates their transport into the nucleus. To determine the structural basis of the recognition of the two classes of NLSs by mammalian importin-alpha, we co-crystallized an N-terminally truncated mouse receptor protein with peptides corresponding to the monopartite NLS from the simian virus 40 (SV40) large T-antigen, and the bipartite NLS from nucleoplasmin. We show that the monopartite SV40 large T-antigen NLS binds to two binding sites on the receptor, similar to what was observed in yeast importin-alpha. The nucleoplasmin NLS-importin-alpha complex shows, for the first time, the mode of binding of bipartite NLSs to the receptor. The two basic clusters in the NLS occupy the two binding sites used by the monopartite NLS, while the sequence linking the two basic clusters is poorly ordered, consistent with its tolerance to mutations. The structures explain the structural basis for binding of diverse NLSs to the sole receptor protein.
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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1EJL is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EJL OCA].
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[[Category: Large Structures]]
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[[Category: Macaca mulatta polyomavirus 1]]
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==Reference==
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Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-alpha., Fontes MR, Teh T, Kobe B, J Mol Biol. 2000 Apr 14;297(5):1183-94. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10764582 10764582]
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[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Protein complex]]
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[[Category: Fontes MR]]
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[[Category: Fontes, M R.]]
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[[Category: Kobe B]]
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[[Category: Kobe, B.]]
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[[Category: Teh T]]
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[[Category: Teh, T.]]
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[[Category: importin alpha/karyopherin alpha; nuclear localization sequence (nls) recognition; simian virus (sv40) large t-antigen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:56:27 2008''
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Current revision

MOUSE IMPORTIN ALPHA-SV40 LARGE T ANTIGEN NLS PEPTIDE COMPLEX

PDB ID 1ejl

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