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4rxh

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Revision as of 10:24, 1 May 2019

Crystal Structure of Importin-alpha from Neurospora crassa complexed with SV40NLS

Structural highlights

4rxh is a 3 chain structure with sequence from Chrysonilia crassa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1ejl
Gene:	3H10.030 (Chrysonilia crassa)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] Isoform 17kT antigen targets host RBL2 for degradation and promotes cell proliferation. Transactivates host cyclin A promoter through its J domain.^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14]

Publication Abstract from PubMed

Neurospora crassa is a filamentous fungus that has been extensively studied as a model organism for eukaryotic biology, providing fundamental insights into cellular processes such as cell signaling, growth and differentiation. To advance in the study of this multicellular organism, an understanding of the specific mechanisms for protein transport into the cell nucleus is essential. Importin-alpha (Imp-alpha) is the receptor for cargo proteins that contain specific nuclear localization signals (NLSs) that play a key role in the classical nuclear import pathway. Structures of Imp-alpha from different organisms (yeast, rice, mouse, and human) have been determined, revealing that this receptor possesses a conserved structural scaffold. However, recent studies have demonstrated that the Impalpha mechanism of action may vary significantly for different organisms or for different isoforms from the same organism. Therefore, structural, functional, and biophysical characterization of different Impalpha proteins is necessary to understand the selectivity of nuclear transport. Here, we determined the first crystal structure of an Impalpha from a filamentous fungus which is also the highest resolution Impalpha structure already solved to date (1.75 A). In addition, we performed calorimetric analysis to determine the affinity and thermodynamic parameters of the interaction between Imp-alpha and the classical SV40 NLS peptide. The comparison of these data with previous studies on Impalpha proteins led us to demonstrate that N. crassa Imp-alpha possess specific features that are distinct from mammalian Imp-alpha but exhibit important similarities to rice Imp-alpha, particularly at the minor NLS binding site.

Structure of Importin-alpha from a Filamentous Fungus in Complex with a Classical Nuclear Localization Signal.,Bernardes NE, Takeda AA, Dreyer TR, Freitas FZ, Bertolini MC, Fontes MR PLoS One. 2015 Jun 19;10(6):e0128687. doi: 10.1371/journal.pone.0128687., eCollection 2015. PMID:26091498^[15]

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

References

↑ Damania B, Alwine JC. TAF-like function of SV40 large T antigen. Genes Dev. 1996 Jun 1;10(11):1369-81. PMID:8647434
↑ Damania B, Lieberman P, Alwine JC. Simian virus 40 large T antigen stabilizes the TATA-binding protein-TFIIA complex on the TATA element. Mol Cell Biol. 1998 Jul;18(7):3926-35. PMID:9632777
↑ Zalvide J, Stubdal H, DeCaprio JA. The J domain of simian virus 40 large T antigen is required to functionally inactivate RB family proteins. Mol Cell Biol. 1998 Mar;18(3):1408-15. PMID:9488456
↑ Skoczylas C, Henglein B, Rundell K. PP2A-dependent transactivation of the cyclin A promoter by SV40 ST is mediated by a cell cycle-regulated E2F site. Virology. 2005 Feb 20;332(2):596-601. PMID:15680424 doi:10.1016/j.virol.2004.12.017
↑ Welcker M, Clurman BE. The SV40 large T antigen contains a decoy phosphodegron that mediates its interactions with Fbw7/hCdc4. J Biol Chem. 2005 Mar 4;280(9):7654-8. Epub 2004 Dec 20. PMID:15611062 doi:10.1074/jbc.M413377200
↑ Valls E, Blanco-Garcia N, Aquizu N, Piedra D, Estaras C, de la Cruz X, Martinez-Balbas MA. Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation. Nucleic Acids Res. 2007;35(6):1958-68. Epub 2007 Mar 6. PMID:17341466 doi:gkl1113
↑ Hein J, Boichuk S, Wu J, Cheng Y, Freire R, Jat PS, Roberts TM, Gjoerup OV. Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol. 2009 Jan;83(1):117-27. doi: 10.1128/JVI.01515-08. Epub 2008 Oct 15. PMID:18922873 doi:10.1128/JVI.01515-08
↑ Damania B, Alwine JC. TAF-like function of SV40 large T antigen. Genes Dev. 1996 Jun 1;10(11):1369-81. PMID:8647434
↑ Damania B, Lieberman P, Alwine JC. Simian virus 40 large T antigen stabilizes the TATA-binding protein-TFIIA complex on the TATA element. Mol Cell Biol. 1998 Jul;18(7):3926-35. PMID:9632777
↑ Zalvide J, Stubdal H, DeCaprio JA. The J domain of simian virus 40 large T antigen is required to functionally inactivate RB family proteins. Mol Cell Biol. 1998 Mar;18(3):1408-15. PMID:9488456
↑ Skoczylas C, Henglein B, Rundell K. PP2A-dependent transactivation of the cyclin A promoter by SV40 ST is mediated by a cell cycle-regulated E2F site. Virology. 2005 Feb 20;332(2):596-601. PMID:15680424 doi:10.1016/j.virol.2004.12.017
↑ Welcker M, Clurman BE. The SV40 large T antigen contains a decoy phosphodegron that mediates its interactions with Fbw7/hCdc4. J Biol Chem. 2005 Mar 4;280(9):7654-8. Epub 2004 Dec 20. PMID:15611062 doi:10.1074/jbc.M413377200
↑ Valls E, Blanco-Garcia N, Aquizu N, Piedra D, Estaras C, de la Cruz X, Martinez-Balbas MA. Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation. Nucleic Acids Res. 2007;35(6):1958-68. Epub 2007 Mar 6. PMID:17341466 doi:gkl1113
↑ Hein J, Boichuk S, Wu J, Cheng Y, Freire R, Jat PS, Roberts TM, Gjoerup OV. Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol. 2009 Jan;83(1):117-27. doi: 10.1128/JVI.01515-08. Epub 2008 Oct 15. PMID:18922873 doi:10.1128/JVI.01515-08
↑ Bernardes NE, Takeda AA, Dreyer TR, Freitas FZ, Bertolini MC, Fontes MR. Structure of Importin-alpha from a Filamentous Fungus in Complex with a Classical Nuclear Localization Signal. PLoS One. 2015 Jun 19;10(6):e0128687. doi: 10.1371/journal.pone.0128687., eCollection 2015. PMID:26091498 doi:http://dx.doi.org/10.1371/journal.pone.0128687

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4rxh"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Importin-alpha from Neurospora crassa complexed with SV40NLS==
-<StructureSection load='4rxh' size='340' side='right' caption='[[4rxh]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
+<StructureSection load='4rxh' size='340' side='right'caption='[[4rxh]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4rxh]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RXH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4rxh]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Chrysonilia_crassa Chrysonilia crassa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RXH FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ejl|1ejl]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">3H10.030 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5141 Chrysonilia crassa])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rxh OCA], [http://pdbe.org/4rxh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rxh RCSB], [http://www.ebi.ac.uk/pdbsum/4rxh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rxh ProSAT]</span></td></tr>
 </table>
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 4rxh" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Importin|Importin]]
+*[[Large T Antigen|Large T Antigen]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Chrysonilia crassa]]
+[[Category: Large Structures]]
 [[Category: Bernardes, N E]]
 [[Category: Fontes, M R.M]]

4rxh

From Proteopedia

Revision as of 10:24, 1 May 2019

Crystal Structure of Importin-alpha from Neurospora crassa complexed with SV40NLS

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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