6q6r

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Recognition of different base tetrads by RHAU: X-ray crystal structure of G4 recognition motif bound to the 3-end tetrad of a DNA G-quadruplex

Structural highlights

6q6r is a 8 chain structure with sequence from Homo sapiens and Unidentified. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.5Å
Ligands:K
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

G-quadruplexes (G4) are secondary structures of nucleic acids that can form in cells and have diverse biological functions. Several biologically important proteins interact with G-quadruplexes, of which RHAU - a helicase from the DEAH-box superfamily, was shown to bind and unwind G-quadruplexes efficiently. We report a X-ray co-crystal structure at 1.5 A resolution of an N-terminal fragment of RHAU bound to the exposed tetrad of a parallel-stranded G-quadruplex. The RHAU peptide folds into an L-shaped alpha-helix, and binds to the G-quadruplex through pi-stacking and electrostatic interactions. X-ray crystal structure of our complex identified key amino acid residues important for G-quadruplex-peptide binding interaction at the 3'-end G*G*G*G tetrad. Together with previous solution and crystal structures of RHAU bound to the 5'-end G*G*G*G and G*G*A*T tetrads, our crystal structure highlights the occurrence of a robust G-quadruplex recognition motif within RHAU that can adapt to different accessible tetrads.

Recognition of different base tetrads by RHAU: X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex.,Heddi B, Vee Cheong V, Schmitt E, Mechulam Y, Tuan Phan A J Struct Biol. 2019 Oct 3. pii: S1047-8477(19)30210-2. doi:, 10.1016/j.jsb.2019.10.001. PMID:31586599[10]

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

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See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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
  8. ↑ 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
  9. ↑ 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
  10. ↑ Heddi B, Vee Cheong V, Schmitt E, Mechulam Y, Tuan Phan A. Recognition of different base tetrads by RHAU: X-ray crystal structure of the G4 recognition motif bound to the 3'-end tetrad of a DNA G-quadruplex. J Struct Biol. 2019 Oct 3. pii: S1047-8477(19)30210-2. doi:, 10.1016/j.jsb.2019.10.001. PMID:31586599 doi:http://dx.doi.org/10.1016/j.jsb.2019.10.001

Contents


PDB ID 6q6r

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