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2n21

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Revision as of 13:19, 10 May 2017

Solution structure of complex between DNA G-quadruplex and G-quadruplex recognition domain of RHAU

Structural highlights

2n21 is a 2 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DHX36_HUMAN] Proposed to have a global role in regulating mRNA expression including transcriptional regulation and mRNA stability. Binds with high affinity to and resolves tetramolecular RNA and DNA quadruplex structures. Unwinds intramolecular quadruplexes derived from the ZIC1 and the MYC promoters. Binds to quadruplex structures in the promoters of YY1 and ALPL genes and regulates their expression. Binds to telomerase RNA template component (TERC) 5'-end (nucleotides 1-43) and unwinds an internal quadruplex formation in TERC 5'-end to promote P1 helix formation; the P1 helix acts as a template boundary ensuring accurate reverse transcription and is disrupted by quadruplex formation. May be involved in regulation of telomere length. Plays a role in degradation and deadenylation of mRNAs containing in their 3'-UTR the consensus ARE sequence element. May function in sex development and spermatogenesis. May play a role in ossification.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

Publication Abstract from PubMed

Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex-protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds to and resolves parallel-stranded G-quadruplexes. Here we identified an 18-amino acid G-quadruplex-binding domain of RHAU and determined the structure of this peptide bound to a parallel DNA G-quadruplex. Our structure explains how RHAU specifically recognizes parallel G-quadruplexes. The peptide covers a terminal guanine base tetrad (G-tetrad), and clamps the G-quadruplex using three-anchor-point electrostatic interactions between three positively charged amino acids and negatively charged phosphate groups. This binding mode is strikingly similar to that of most ligands selected for specific G-quadruplex targeting. Binding to an exposed G-tetrad represents a simple and efficient way to specifically target G-quadruplex structures.

Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex.,Heddi B, Cheong VV, Martadinata H, Phan AT Proc Natl Acad Sci U S A. 2015 Jul 20. pii: 201422605. PMID:26195789^[10]

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

References

↑ Fu JJ, Li LY, Lu GX. Molecular cloning and characterization of human DDX36 and mouse Ddx36 genes, new members of the DEAD/H box superfamily. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2002, Sep;34(5):655-61. PMID:12198572
↑ Tran H, Schilling M, Wirbelauer C, Hess D, Nagamine Y. Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU. Mol Cell. 2004 Jan 16;13(1):101-11. PMID:14731398
↑ Vaughn JP, Creacy SD, Routh ED, Joyner-Butt C, Jenkins GS, Pauli S, Nagamine Y, Akman SA. The DEXH protein product of the DHX36 gene is the major source of tetramolecular quadruplex G4-DNA resolving activity in HeLa cell lysates. J Biol Chem. 2005 Nov 18;280(46):38117-20. Epub 2005 Sep 7. PMID:16150737 doi:http://dx.doi.org/10.1074/jbc.C500348200
↑ Creacy SD, Routh ED, Iwamoto F, Nagamine Y, Akman SA, Vaughn JP. G4 resolvase 1 binds both DNA and RNA tetramolecular quadruplex with high affinity and is the major source of tetramolecular quadruplex G4-DNA and G4-RNA resolving activity in HeLa cell lysates. J Biol Chem. 2008 Dec 12;283(50):34626-34. doi: 10.1074/jbc.M806277200. Epub 2008, Oct 7. PMID:18842585 doi:http://dx.doi.org/10.1074/jbc.M806277200
↑ Lattmann S, Giri B, Vaughn JP, Akman SA, Nagamine Y. Role of the amino terminal RHAU-specific motif in the recognition and resolution of guanine quadruplex-RNA by the DEAH-box RNA helicase RHAU. Nucleic Acids Res. 2010 Oct;38(18):6219-33. doi: 10.1093/nar/gkq372. Epub 2010, May 14. PMID:20472641 doi:http://dx.doi.org/10.1093/nar/gkq372
↑ Sexton AN, Collins K. The 5' guanosine tracts of human telomerase RNA are recognized by the G-quadruplex binding domain of the RNA helicase DHX36 and function to increase RNA accumulation. Mol Cell Biol. 2011 Feb;31(4):736-43. doi: 10.1128/MCB.01033-10. Epub 2010 Dec, 13. PMID:21149580 doi:http://dx.doi.org/10.1128/MCB.01033-10
↑ Giri B, Smaldino PJ, Thys RG, Creacy SD, Routh ED, Hantgan RR, Lattmann S, Nagamine Y, Akman SA, Vaughn JP. G4 resolvase 1 tightly binds and unwinds unimolecular G4-DNA. Nucleic Acids Res. 2011 Sep 1;39(16):7161-78. doi: 10.1093/nar/gkr234. Epub 2011 , May 17. PMID:21586581 doi:http://dx.doi.org/10.1093/nar/gkr234
↑ Huang W, Smaldino PJ, Zhang Q, Miller LD, Cao P, Stadelman K, Wan M, Giri B, Lei M, Nagamine Y, Vaughn JP, Akman SA, Sui G. Yin Yang 1 contains G-quadruplex structures in its promoter and 5'-UTR and its expression is modulated by G4 resolvase 1. Nucleic Acids Res. 2012 Feb;40(3):1033-49. doi: 10.1093/nar/gkr849. Epub 2011 Oct, 12. PMID:21993297 doi:http://dx.doi.org/10.1093/nar/gkr849
↑ Booy EP, Meier M, Okun N, Novakowski SK, Xiong S, Stetefeld J, McKenna SA. The RNA helicase RHAU (DHX36) unwinds a G4-quadruplex in human telomerase RNA and promotes the formation of the P1 helix template boundary. Nucleic Acids Res. 2012 May;40(9):4110-24. doi: 10.1093/nar/gkr1306. Epub 2012, Jan 11. PMID:22238380 doi:http://dx.doi.org/10.1093/nar/gkr1306
↑ Heddi B, Cheong VV, Martadinata H, Phan AT. Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex. Proc Natl Acad Sci U S A. 2015 Jul 20. pii: 201422605. PMID:26195789 doi:http://dx.doi.org/10.1073/pnas.1422605112

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/2n21"

Categories: Cheong, V V | Heddi, B | Martadinata, H | Phan, A T | Hydrolase-dna complex

@@ Line 1: / Line 1: @@
 ==Solution structure of complex between DNA G-quadruplex and G-quadruplex recognition domain of RHAU==
 <StructureSection load='2n21' size='340' side='right' caption='[[2n21]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2n21]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N21 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N21 FirstGlance]. <br>
-</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=2n21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n21 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2n21 RCSB], [http://www.ebi.ac.uk/pdbsum/2n21 PDBsum]</span></td></tr>
+</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=2n21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n21 OCA], [http://pdbe.org/2n21 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n21 RCSB], [http://www.ebi.ac.uk/pdbsum/2n21 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n21 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2n21" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2n21

From Proteopedia

Revision as of 13:19, 10 May 2017

Solution structure of complex between DNA G-quadruplex and G-quadruplex recognition domain of RHAU

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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