6up4: Difference between revisions

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<StructureSection load='6up4' size='340' side='right'caption='[[6up4]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
<StructureSection load='6up4' size='340' side='right'caption='[[6up4]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6up4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UP4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UP4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6up4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UP4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UP4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.4&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dhx36 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6up4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6up4 OCA], [http://pdbe.org/6up4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6up4 RCSB], [http://www.ebi.ac.uk/pdbsum/6up4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6up4 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=6up4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6up4 OCA], [https://pdbe.org/6up4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6up4 RCSB], [https://www.ebi.ac.uk/pdbsum/6up4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6up4 ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/DHX36_MOUSE DHX36_MOUSE] Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures (PubMed:25611385). Plays a role in many biological processes such as genomic integrity, gene expression regulations and as a sensor to initiate antiviral responses (PubMed:21703541, PubMed:21590736). G4 structures correspond to helical structures containing guanine tetrads (By similarity). Binds with high affinity to and unwinds G4 structures that are formed in nucleic acids (G4-ADN and G4-RNA) (By similarity). Plays a role in genomic integrity (By similarity). Converts the G4-RNA structure present in telomerase RNA template component (TREC) into a double-stranded RNA to promote P1 helix formation that acts as a template boundary ensuring accurate reverse transcription (By similarity). Plays a role in transcriptional regulation. Resolves G4-DNA structures in promoters of genes, such as YY1, KIT/c-kit and ALPL and positively regulates their expression (PubMed:25611385) (By similarity). Plays a role in post-transcriptional regulation (By similarity). Unwinds a G4-RNA structure located in the 3'-UTR polyadenylation site of the pre-mRNA TP53 and stimulates TP53 pre-mRNA 3'-end processing in response to ultraviolet (UV)-induced DNA damage (By similarity). Binds to the precursor-microRNA-134 (pre-miR-134) terminal loop and regulates its transport into the synapto-dendritic compartment (By similarity). Involved in the pre-miR-134-dependent inhibition of target gene expression and the control of dendritic spine size (By similarity). Plays a role in the regulation of cytoplasmic mRNA translation and mRNA stability (By similarity). Binds to both G4-RNA structures and alternative non-quadruplex-forming sequence within the 3'-UTR of the PITX1 mRNA regulating negatively PITX1 protein expression (By similarity). Binds to both G4-RNA structure in the 5'-UTR and AU-rich elements (AREs) localized in the 3'-UTR of NKX2-5 mRNA to either stimulate protein translation or induce mRNA decay in an ELAVL1-dependent manner, respectively (By similarity). Binds also to ARE sequences present in several mRNAs mediating exosome-mediated 3'-5' mRNA degradation (By similarity). Involved in cytoplasmic urokinase-type plasminogen activator (uPA) mRNA decay (By similarity). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (PubMed:21703541). Required for the early embryonic development and hematopoiesis (PubMed:22422825). Involved in the regulation of cardioblast differentiation and proliferation during heart development (PubMed:26489465). Involved in spermatogonia differentiation (PubMed:25611385). May play a role in ossification (PubMed:21590736).[UniProtKB:D4A2Z8][UniProtKB:Q05B79][UniProtKB:Q9H2U1]<ref>PMID:21590736</ref> <ref>PMID:21703541</ref> <ref>PMID:22422825</ref> <ref>PMID:25611385</ref> <ref>PMID:26489465</ref>
The DEAH/RHA helicase DHX36 has been linked to cellular RNA and DNA quadruplex structures and to AU-rich RNA elements. In vitro, DHX36 remodels DNA and RNA quadruplex structures and unwinds DNA duplexes in an ATP-dependent manner. DHX36 contains the superfamily 2 helicase core and several auxiliary domains that are conserved in orthologs of the enzyme. The role of these auxiliary domains for the enzymatic function of DHX36 is not well understood. Here, we combine structural and biochemical studies to define the function of three auxiliary domains that contact nucleic acid. We first report the crystal structure of mouse DHX36 bound to ADP. The structure reveals an overall architecture of mouse DHX36 that is similar to previously reported architectures of fly and bovine DHX36. In addition, our structure shows conformational changes that accompany stages of the ATP-binding and hydrolysis cycle. We then examine the roles of the DHX36-specific motif (DSM), the OB-fold, and a conserved beta-hairpin (beta-HP) in mouse DHX36 in the remodeling of RNA structures. We demonstrate and characterize RNA duplex unwinding for DHX36 and examine the remodeling of inter- and intramolecular RNA quadruplex structures. We find that the DSM not only functions as a quadruplex binding adaptor but also promotes the remodeling of RNA duplex and quadruplex structures. The OB-fold and the beta-HP contribute to RNA binding. Both domains are also essential for remodeling RNA quadruplex and duplex structures. Our data reveal roles of auxiliary domains for multiple steps of the nucleic acid remodeling reactions.


Function of Auxiliary Domains of the DEAH/RHA Helicase DHX36 in RNA Remodeling.,Srinivasan S, Liu Z, Chuenchor W, Xiao TS, Jankowsky E J Mol Biol. 2020 Feb 19. pii: S0022-2836(20)30155-8. doi:, 10.1016/j.jmb.2020.02.005. PMID:32087197<ref>PMID:32087197</ref>
==See Also==
 
*[[Helicase 3D structures|Helicase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6up4" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: Liu, Z]]
[[Category: Liu Z]]
[[Category: Xiao, T S]]
[[Category: Xiao TS]]
[[Category: Atp-dependent]]
[[Category: Dna-binding]]
[[Category: G4 resolvase]]
[[Category: Helicase]]
[[Category: Rna binding protein]]
[[Category: Rna-binding]]

Latest revision as of 17:57, 13 March 2024

Crystal structure of the murine DHX36 helicase in complex with ADPCrystal structure of the murine DHX36 helicase in complex with ADP

Structural highlights

6up4 is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DHX36_MOUSE Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures (PubMed:25611385). Plays a role in many biological processes such as genomic integrity, gene expression regulations and as a sensor to initiate antiviral responses (PubMed:21703541, PubMed:21590736). G4 structures correspond to helical structures containing guanine tetrads (By similarity). Binds with high affinity to and unwinds G4 structures that are formed in nucleic acids (G4-ADN and G4-RNA) (By similarity). Plays a role in genomic integrity (By similarity). Converts the G4-RNA structure present in telomerase RNA template component (TREC) into a double-stranded RNA to promote P1 helix formation that acts as a template boundary ensuring accurate reverse transcription (By similarity). Plays a role in transcriptional regulation. Resolves G4-DNA structures in promoters of genes, such as YY1, KIT/c-kit and ALPL and positively regulates their expression (PubMed:25611385) (By similarity). Plays a role in post-transcriptional regulation (By similarity). Unwinds a G4-RNA structure located in the 3'-UTR polyadenylation site of the pre-mRNA TP53 and stimulates TP53 pre-mRNA 3'-end processing in response to ultraviolet (UV)-induced DNA damage (By similarity). Binds to the precursor-microRNA-134 (pre-miR-134) terminal loop and regulates its transport into the synapto-dendritic compartment (By similarity). Involved in the pre-miR-134-dependent inhibition of target gene expression and the control of dendritic spine size (By similarity). Plays a role in the regulation of cytoplasmic mRNA translation and mRNA stability (By similarity). Binds to both G4-RNA structures and alternative non-quadruplex-forming sequence within the 3'-UTR of the PITX1 mRNA regulating negatively PITX1 protein expression (By similarity). Binds to both G4-RNA structure in the 5'-UTR and AU-rich elements (AREs) localized in the 3'-UTR of NKX2-5 mRNA to either stimulate protein translation or induce mRNA decay in an ELAVL1-dependent manner, respectively (By similarity). Binds also to ARE sequences present in several mRNAs mediating exosome-mediated 3'-5' mRNA degradation (By similarity). Involved in cytoplasmic urokinase-type plasminogen activator (uPA) mRNA decay (By similarity). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (PubMed:21703541). Required for the early embryonic development and hematopoiesis (PubMed:22422825). Involved in the regulation of cardioblast differentiation and proliferation during heart development (PubMed:26489465). Involved in spermatogonia differentiation (PubMed:25611385). May play a role in ossification (PubMed:21590736).[UniProtKB:D4A2Z8][UniProtKB:Q05B79][UniProtKB:Q9H2U1][1] [2] [3] [4] [5]

See Also

References

  1. ↑ Kim HN, Lee JH, Bae SC, Ryoo HM, Kim HH, Ha H, Lee ZH. Histone deacetylase inhibitor MS-275 stimulates bone formation in part by enhancing Dhx36-mediated TNAP transcription. J Bone Miner Res. 2011 Sep;26(9):2161-73. PMID:21590736 doi:10.1002/jbmr.426
  2. ↑ Zhang Z, Kim T, Bao M, Facchinetti V, Jung SY, Ghaffari AA, Qin J, Cheng G, Liu YJ. DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Immunity. 2011 Jun 24;34(6):866-78. PMID:21703541 doi:10.1016/j.immuni.2011.03.027
  3. ↑ Lai JC, Ponti S, Pan D, Kohler H, Skoda RC, Matthias P, Nagamine Y. The DEAH-box helicase RHAU is an essential gene and critical for mouse hematopoiesis. Blood. 2012 May 3;119(18):4291-300. PMID:22422825 doi:10.1182/blood-2011-08-362954
  4. ↑ Gao X, Ma W, Nie J, Zhang C, Zhang J, Yao G, Han J, Xu J, Hu B, Du Y, Shi Q, Yang Z, Huang X, Zhang Y. A G-quadruplex DNA structure resolvase, RHAU, is essential for spermatogonia differentiation. Cell Death Dis. 2015 Jan 22;6(1):e1610. PMID:25611385 doi:10.1038/cddis.2014.571
  5. ↑ Nie J, Jiang M, Zhang X, Tang H, Jin H, Huang X, Yuan B, Zhang C, Lai JC, Nagamine Y, Pan D, Wang W, Yang Z. Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart Development. Cell Rep. 2015 Oct 27;13(4):723-732. PMID:26489465 doi:10.1016/j.celrep.2015.09.043

6up4, resolution 2.40Å

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