2020同步年報

Life Science 043 showed that the binding of two Z1 molecules at the termi- nal CTG repeat motifs induces many surprising features that include mainly formation of a distorted DNA backbone con- formation along with the flipping of a mismatched thymine base away from the backbone that ultimately resulted in a four-way-junction structure of a novel type. The Z1 inter- calation caused the four chains of DNA to adopt a double U-shaped head-to-head topology conformation and result- ed in the crossing of each strand at the intersection point ( Fig. 1(d) ). Upon further analysis of the structure, Hou’s team learned that this central crossing is stabilized with two stacked G:C base pairs in the central region that can rotate by ca. 50° with respect to each other and form an X-shaped structure due to the alignment of two G•C•G•C tetrads into a nonplanar structure ( Fig. 1(e) ). The stacking of G:C pairs on both sides resulted in the formation of an apparently continuous duplex DNA. They further observed that the coordination of four Co II metal ions between N7 atoms of guanines can strongly preserve the central junction site. As this study identifies the structural basis of a small mol- ecule to induce higher-order structure formation, the information obtained from this work might be applicable in designing more sequence-specific ligands targeting re- peat-associated atypical DNA structures, particularly those associated with neurological disorders. In summary, the findings from Hou and his team deepen our understanding regarding the molecular-level mechanism of the formation of higher-order atypical DNA conformations through ligand binding and its supramolecular interactions. Because of the flexibility of DNA to adopt a specific conformation based on a specific sequence or ligand binding, the authors stipu- lated that the results from this study can be useful also in DNA nanotechnology-based sensors or tweezers develop- ment. (Reported by Roshan Satange, National Chung Hsing University) This report features the work of Ming-Hon Hou, Steven C. Zimmerman and their collaborators published in the J. Am. Chem. Soc. 142 , 11165 (2020). TPS 05A Protein Microcrystallography TLS 15A1 IASW – Biopharmaceutical Protein Crys- tallography • Protein Crystallography • Biological Macromolecules, Unusual DNA Structures, Life Science References 1. S. M. Mirkin, Nature 447 , 932 (2007). 2. R. Satange, C.-K. Chang, M.-H. Hou, Nucleic Acids Res. 46 , 6416 (2018). 3. J. F. Arambula, S. R. Ramisetty, A. M. Baranger, S. C. Zimmerman, Proc. Nati. Acad. Sci. USA 106 , 16068 (2009). 4. C.-M. Chien, P.-C. Wu, R. Satange, C.-C. Chang, Z.-L. Lai, L. D. Hagler, S. C. Zimmerman, M.-H. Hou, J. Am. Chem. Soc. 142 , 11165 (2020).