6up4

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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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