Single-Molecule Biophysics: My research group aims to understand molecular mechanisms of “biological process on cell membranes”, which have been largely shunted aside in spite of their biological and practical importance. My group employs an arsenal of single-molecule techniques to observe both conformational changes and consequential function of the membrane proteins, which allows direct determination of their structure-function relationship. We recently reported the disassembly mechanism of the SNARE complex by a proteasome system (20S complex), providing insights into how AAA+ ATPases tightly couple their ATP hydrolysis and unfolding of protein substrates (JACS 2013 and Science 2015). In addition, my research group is pioneering an approach where we apply mechanical tension to the integral membrane proteins while observing their function, which allows determination of the energy landscape governing conformational changes of the membrane proteins (Nat. Comm. 2013, 2014 and Nat. Chem. Biol. 2015). This series of works is being supported by the National Creative Research Initiative Program (창의적연구진흥과제, 단분자시스템생물학 연구단).
Development of Tools for Precision Medicine: My research group is also interested in development of new single-molecule tools for biochemists and molecular biologists. We recently developed single-molecule version of co-immunoprecipitation (co-IP) analysis (Nat. Comm. 2013, Nat. Prot. 2013, JACS 2016). In molecular biology, the co-IP analysis has been the gold standard of determining protein-protein interactions (PPIs) for several decades. By adopting single-molecule fluorescence microscopy as the detection method (instead of SDS PAGE-gel and western blotting), we have improved the sensitivity and time-resolution of the co-IP analysis by five orders of magnitude, respectively. With the extreme sensitivity and quantitativeness of the developed tool, we demonstrate development of PPI biomarkers that allow precision prediction of drug responses of individual tumors, even in cancer types without actionable genomic mutations. Thus, this suggests a path toward “personalized diagnosis of cancers at the PPI level”, which would expand the concept and scope of the targeted cancer therapy. This work is supported by the Samsung Science and Technology Foundation (삼성미래기술육성재단).
- Shon, M. J., Kim, H., & Yoon, T. Y. (2018). Focused clamping of a single neuronal SNARE complex by complexin under high mechanical tension. Nature Communications, 9(1), 3639.
- Lee, H. W., Choi, B., Kang, H. N., Kim, H., Min, A., Cha, M., ... & Yun, M. R. (2018). "Profiling of protein–protein interactions via single-molecule techniques predicts the dependence of cancers on growth-factor receptors" Nature Biomedical Engineering, 2(4), 239.
- J.-K. Ryu, S. J. Kim, S.-H. Rah, J. I. Kang, H. E. Jung, D. Lee, H. K. Lee, J.-O. Lee, B. S. Park, T.-Y. Yoon, H. M. Kim (2017) “Reconstruction of LPS Transfer Cascade Reveals Structural Determinants within LBP, CD14, and TLR4-MD2 for Efficient LPS Recognition and Transfer” Immunity 46, 38-50
- J. Yoo, T.-S. Lee, B. Choi, M. J. Shon, T.-Y. Yoon (2016) “Observing extremely weak protein-protein interactions with conventional single-molecule fluorescence microscopy” Journal of the American Chemical Society 138, 14238-147241
- D. Min, R. Jefferson, J. Bowie, & T.-Y. Yoon (2015) “Mapping the energy landscape for second-stage folding of a single membrane protein” Nature Chemical Biology 11, 981-987