This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4a4d

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

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?)

Views

Personal tools

Navigation

Search

Toolbox