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4a4d

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Revision as of 16:06, 4 August 2016

Crystal structure of the N-terminal domain of the Human DEAD-BOX RNA helicase DDX5 (P68)

Structural highlights

4a4d is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:	RNA helicase, with EC number 3.6.4.13
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DDX5_HUMAN] Involved in the alternative regulation of pre-mRNA splicing; its RNA helicase activity is necessary for increasing tau exon 10 inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre-mRNA in the stem-loop region downstream of exon 10. The rate of ATP hydrolysis is highly stimulated by single-stranded RNA. Involved in transcriptional regulation; the function is independent of the RNA helicase activity. Transcriptional coactivator for estrogen receptor ESR1 and androgen receptor AR. Increases ESR1 AF-1 domain-mediated transactivation and ESR1 AF-1 and AF-2 domains transcriptional synergistic activity. Synergizes with DDX17 and SRA1 RNA to activate MYOD1 transcriptional activity and involved in skeletal muscle differentiation. Transcriptional coactivator for p53/TP53 and involved in p53/TP53 transcriptional response to DNA damage and p53/TP53-dependent apoptosis. Transcriptional coactivator for RUNX2 and involved in regulation of osteoblast differentiation. Acts as transcriptional repressor in a promoter-specicic manner; the function probbaly involves association with histone deacetylases, such as HDAC1.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Publication Abstract from PubMed

RNA helicases of the DEAD (Asp-Glu-Ala-Asp)-box family of proteins are involved in many aspects of RNA metabolism from transcription to RNA decay, but most of them have also been shown to be multifunctional. The DEAD-box helicase DDX5 of host cells has been shown to interact with the RNA-dependent RNA polymerase (NS5B) of HCV (hepatitis C virus). In the present study, we report the presence of two independent NS5B-binding sites in DDX5, one located at the N-terminus and another at the C-terminus. The N-terminal fragment of DDX5, which consists of the first 305 amino acids and shall be referred as DDX5-N, was expressed and crystallized. The crystal structure shows that domain 1 (residues 79-303) of DDX5 contains the typical features found in the structures of other DEAD-box helicases. DDX5-N also contains the highly variable NTR (N-terminal region) of unknown function and the crystal structure reveals structural elements in part of the NTR, namely residues 52-78. This region forms an extensive loop and an alpha-helix. From co-immunoprecipitation experiments, the NTR of DDX5-N was observed to auto-inhibit its interaction with NS5B. Interestingly, the alpha-helix in NTR is essential for this auto-inhibition and seems to mediate the interaction between the highly flexible 1-51 residues in NTR and the NS5B-binding site in DDX5-N. Furthermore, NMR investigations reveal that there is a direct interaction between DDX5 and NS5B in vitro.

The variable N-terminal region of DDX5 contains structural elements and auto-inhibits its interaction with NS5B of hepatitis C virus.,Dutta S, Gupta G, Choi YW, Kotaka M, Fielding BC, Song J, Tan YJ Biochem J. 2012 Aug 15;446(1):37-46. PMID:22640416^[11]

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

References

↑ Endoh H, Maruyama K, Masuhiro Y, Kobayashi Y, Goto M, Tai H, Yanagisawa J, Metzger D, Hashimoto S, Kato S. Purification and identification of p68 RNA helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor alpha. Mol Cell Biol. 1999 Aug;19(8):5363-72. PMID:10409727
↑ Watanabe M, Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y, Suzawa M, Kobayashi Y, Yano T, Yoshikawa H, Masuhiro Y, Kato S. A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor alpha coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA. EMBO J. 2001 Mar 15;20(6):1341-52. PMID:11250900 doi:http://dx.doi.org/10.1093/emboj/20.6.1341
↑ Rossow KL, Janknecht R. Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300. Oncogene. 2003 Jan 9;22(1):151-6. PMID:12527917 doi:http://dx.doi.org/10.1038/sj.onc.1206067
↑ Wilson BJ, Bates GJ, Nicol SM, Gregory DJ, Perkins ND, Fuller-Pace FV. The p68 and p72 DEAD box RNA helicases interact with HDAC1 and repress transcription in a promoter-specific manner. BMC Mol Biol. 2004 Aug 6;5:11. PMID:15298701 doi:http://dx.doi.org/10.1186/1471-2199-5-11
↑ Bates GJ, Nicol SM, Wilson BJ, Jacobs AM, Bourdon JC, Wardrop J, Gregory DJ, Lane DP, Perkins ND, Fuller-Pace FV. The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor. EMBO J. 2005 Feb 9;24(3):543-53. Epub 2005 Jan 20. PMID:15660129 doi:http://dx.doi.org/10.1038/sj.emboj.7600550
↑ Caretti G, Schiltz RL, Dilworth FJ, Di Padova M, Zhao P, Ogryzko V, Fuller-Pace FV, Hoffman EP, Tapscott SJ, Sartorelli V. The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation. Dev Cell. 2006 Oct;11(4):547-60. PMID:17011493 doi:http://dx.doi.org/10.1016/j.devcel.2006.08.003
↑ Clark EL, Coulson A, Dalgliesh C, Rajan P, Nicol SM, Fleming S, Heer R, Gaughan L, Leung HY, Elliott DJ, Fuller-Pace FV, Robson CN. The RNA helicase p68 is a novel androgen receptor coactivator involved in splicing and is overexpressed in prostate cancer. Cancer Res. 2008 Oct 1;68(19):7938-46. doi: 10.1158/0008-5472.CAN-08-0932. PMID:18829551 doi:http://dx.doi.org/10.1158/0008-5472.CAN-08-0932
↑ Jensen ED, Niu L, Caretti G, Nicol SM, Teplyuk N, Stein GS, Sartorelli V, van Wijnen AJ, Fuller-Pace FV, Westendorf JJ. p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation. J Cell Biochem. 2008 Apr 1;103(5):1438-51. PMID:17960593 doi:http://dx.doi.org/10.1002/jcb.21526
↑ Wortham NC, Ahamed E, Nicol SM, Thomas RS, Periyasamy M, Jiang J, Ochocka AM, Shousha S, Huson L, Bray SE, Coombes RC, Ali S, Fuller-Pace FV. The DEAD-box protein p72 regulates ERalpha-/oestrogen-dependent transcription and cell growth, and is associated with improved survival in ERalpha-positive breast cancer. Oncogene. 2009 Nov 19;28(46):4053-64. doi: 10.1038/onc.2009.261. Epub 2009 Aug, 31. PMID:19718048 doi:http://dx.doi.org/10.1038/onc.2009.261
↑ Kar A, Fushimi K, Zhou X, Ray P, Shi C, Chen X, Liu Z, Chen S, Wu JY. RNA helicase p68 (DDX5) regulates tau exon 10 splicing by modulating a stem-loop structure at the 5' splice site. Mol Cell Biol. 2011 May;31(9):1812-21. doi: 10.1128/MCB.01149-10. Epub 2011 Feb, 22. PMID:21343338 doi:http://dx.doi.org/10.1128/MCB.01149-10
↑ Dutta S, Gupta G, Choi YW, Kotaka M, Fielding BC, Song J, Tan YJ. The variable N-terminal region of DDX5 contains structural elements and auto-inhibits its interaction with NS5B of hepatitis C virus. Biochem J. 2012 Aug 15;446(1):37-46. PMID:22640416 doi:10.1042/BJ20120001

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4a4d"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the N-terminal domain of the Human DEAD-BOX RNA helicase DDX5 (P68)==
 <StructureSection load='4a4d' size='340' side='right' caption='[[4a4d]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4a4d]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A4D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A4D FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4a4d]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A4D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A4D FirstGlance]. <br>
 </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_helicase RNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.13 3.6.4.13] </span></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=4a4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a4d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a4d RCSB], [http://www.ebi.ac.uk/pdbsum/4a4d PDBsum]</span></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=4a4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a4d OCA], [http://pdbe.org/4a4d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a4d RCSB], [http://www.ebi.ac.uk/pdbsum/4a4d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a4d ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4a4d" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: RNA helicase]]
 [[Category: Choi, Y W]]

4a4d

From Proteopedia

Revision as of 16:06, 4 August 2016

Crystal structure of the N-terminal domain of the Human DEAD-BOX RNA helicase DDX5 (P68)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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