Structural Basis for the Identification of an i‐Motif Tetraplex Core with a Parallel‐Duplex Junction as a Structural Motif in CCG Triplet Repeats |
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| Authors: | Dr Yi‐Wen Chen Cyong‐Ru Jhan Prof Stephen Neidle Dr Ming‐Hon Hou |
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| Institution: | 1. Institute of Genomics and Bioinformatics and Institute of Biochemistry, National Chung Hsing University, No. 250 Kuo‐Kuang Road, Taichung (Taiwan);2. Department of Life Sciences, National Chung Hsing University, No. 250 Kuo‐Kuang Road, Taichung (Taiwan);3. The School of Pharmacy, University College London, London WC1N 1AX (UK) |
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| 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)3A 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. |
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| Keywords: | DNA structures i‐motifs neurological disease tetraplex structures X‐ray diffraction |
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