Outstanding Publication: TMU Structural Biomedical Research Team Led by Distinguished Chair Professor Andrew H.-J. Wang and Associate Research Fellow Cheng-chung,Lee Gains International Recognition
Distinguished Chair Professor Andrew H.-J. Wang, Academician of the Program in Translational Medicine Ph.D., together with Associate Research Fellow Cheng-Chung Lee, has led the Structural Biomedical Research Team to another internationally recognized achievement. The team has successfully elucidated, for the first time at the atomic level, the molecular mechanism by which antibodies recognize and stabilize left-handed Z-DNA. Their findings were published in the prestigious international journal Nucleic Acids Research (5-Year Impact Factor = 16.8), a leading journal in nucleic acid research. This accomplishment highlights the University’s outstanding research capacity in structural biology and translational medicine.
More than half a century ago, Academician Andrew H.-J. Wang discovered the left-handed helical Z-DNA structure at the Massachusetts Institute of Technology (MIT), overturning the long-held belief that DNA existed only in the right-handed B-DNA form and establishing a milestone in the study of DNA structural diversity.
In this study, the research team integrated AI-assisted antibody engineering, high-resolution X-ray crystallography, and multiple biophysical analytical techniques to successfully determine the complex structure between a Z-DNA–specific antibody (cZ22) and DNA. The study revealed that the antibody recognizes Z-DNA through a “backbone-tracking” mode along the left-handed DNA helix. By clasping the left-handed phosphate backbone and forming cooperative interactions with nucleic acid bases, the antibody stabilizes DNA in the Z-conformation. This work provides the first atomic-level insight into the interaction mechanism between antibodies and Z-DNA.
The structural elucidation of antibody–Z-DNA interactions fills a critical knowledge gap in the molecular recognition mechanisms of left-handed nucleic acids. It also opens new directions for research in gene regulation, antiviral responses, and autoimmune diseases, further demonstrating the University’s continuing leadership, academic strength, and international impact in advancing frontier life science research.
