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Structural basis for the identification of an i-motif tetraplex core with a parallel-duplex junction as a structural motif in CCG triplet repeats.

Chen YW, Jhan CR, Neidle S, Hou MH
Angew Chem Int Ed Engl 53 10682-6 (2014)
Cited: 16 times
EuropePMC logo PMID: 25139267

Abstract

CCG triplet repeats can fold into tetraplex structures, which are associated with the expansion of (CCG)n trinucleotide sequences in certain neurological diseases. These structures are stabilized by intertwining i-motifs. However, the structural basis for tetraplex i-motif formation in CCG triplet repeats remains largely unknown. We report the first crystal structure of a CCG-repeat sequence, which shows that two dT(CCG)3 A strands can associate to form a tetraplex structure with an i-motif core containing four C:C(+) pairs flanked by two G:G homopurine base pairs as a structural motif. The tetraplex core is attached to a short parallel-stranded duplex. Each hairpin itself contains a central CCG loop in which the nucleotides are flipped out and stabilized by stacking interactions. The helical twists between adjacent cytosine residues of this structure in the i-motif core have an average value of 30°, which is greater than those previously reported for i-motif structures.

Reviews - 4pzq mentioned but not cited (1)

  1. Molecular conformations and dynamics of nucleotide repeats associated with neurodegenerative diseases: double helices and CAG hairpin loops. Pan F, Zhang Y, Xu P, Man VH, Roland C, Weninger K, Sagui C. Comput Struct Biotechnol J 19 2819-2832 (2021)

Articles - 4pzq mentioned but not cited (2)

  1. Secondary structural choice of DNA and RNA associated with CGG/CCG trinucleotide repeat expansion rationalizes the RNA misprocessing in FXTAS. Ajjugal Y, Kolimi N, Rathinavelan T. Sci Rep 11 8163 (2021)
  2. CoII(Chromomycin)₂ Complex Induces a Conformational Change of CCG Repeats from i-Motif to Base-Extruded DNA Duplex. Chen YW, Satange R, Wu PC, Jhan CR, Chang CK, Chung KR, Waring MJ, Lin SW, Hsieh LC, Hou MH. Int J Mol Sci 19 E2796 (2018)


Reviews citing this publication (1)

  1. A survey of recent unusual high-resolution DNA structures provoked by mismatches, repeats and ligand binding. Satange R, Chang CK, Hou MH. Nucleic Acids Res 46 6416-6434 (2018)

Articles citing this publication (12)

  1. i-Motif DNA: structural features and significance to cell biology. Abou Assi H, Garavís M, González C, Damha MJ. Nucleic Acids Res 46 8038-8056 (2018)
  2. Loop nucleotides impact the stability of intrastrand i-motif structures at neutral pH. Fujii T, Sugimoto N. Phys Chem Chem Phys 17 16719-16722 (2015)
  3. Induced-Fit Recognition of CCG Trinucleotide Repeats by a Nickel-Chromomycin Complex Resulting in Large-Scale DNA Deformation. Tseng WH, Chang CK, Wu PC, Hu NJ, Lee GH, Tzeng CC, Neidle S, Hou MH. Angew Chem Int Ed Engl 56 8761-8765 (2017)
  4. Parity-dependent hairpin configurations of repetitive DNA sequence promote slippage associated with DNA expansion. Huang TY, Chang CK, Kao YF, Chin CH, Ni CW, Hsu HY, Hu NJ, Hsieh LC, Chou SH, Lee IR, Hou MH. Proc Natl Acad Sci U S A 114 9535-9540 (2017)
  5. Thiazole orange as a fluorescent probe: Label-free and selective detection of silver ions based on the structural change of i-motif DNA at neutral pH. Kang BH, Gao ZF, Li N, Shi Y, Li NB, Luo HQ. Talanta 156-157 141-146 (2016)
  6. Selective recognition and stabilization of new ligands targeting the potassium form of the human telomeric G-quadruplex DNA. Lin YH, Chuang SM, Wu PC, Chen CL, Jeyachandran S, Lo SC, Huang HS, Hou MH. Sci Rep 6 31019 (2016)
  7. Stabilization of Telomeric I-Motif Structures by (2'S)-2'-Deoxy-2'-C-Methylcytidine Residues. Aviñó A, Dellafiore M, Gargallo R, González C, Iribarren AM, Montserrat J, Eritja R. Chembiochem 18 1123-1128 (2017)
  8. Structural Implications of Homopyrimidine Base Pairs in the Parallel-Stranded d(YGA) Motif. Tripathi S, Paukstelis PJ. Chembiochem 17 1177-1183 (2016)
  9. Drug design and DNA structural research inspired by the Neidle laboratory: DNA minor groove binding and transcription factor inhibition by thiophene diamidines. Ogbonna EN, Paul A, Ross Terrell J, Fang Z, Chen C, Poon GMK, Boykin DW, Wilson WD. Bioorg Med Chem 68 116861 (2022)
  10. The novel double-folded structure of d(GCATGCATGC): a possible model for triplet-repeat sequences. Thirugnanasambandam A, Karthik S, Mandal PK, Gautham N. Acta Crystallogr D Biol Crystallogr 71 2119-2126 (2015)
  11. Crystal Structure of an i-Motif from the HRAS Oncogene Promoter. Li KS, Jordan D, Lin LY, McCarthy SE, Schneekloth JS, Yatsunyk LA. Angew Chem Int Ed Engl 62 e202301666 (2023)
  12. Dimeric structures of DNA ATTTC repeats promoted by divalent cations. Trajkovski M, Pastore A, Plavec J. Nucleic Acids Res 52 1591-1601 (2024)


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