Human cells store approximately 3 billion base pairs of DNA in the nucleus, which would be roughly 2 meters long if fully extended. However, the DNA is contained within the nucleus, which is only around 6 μm in diameter, due to compaction by packaging it as chromatin. Chromatin consists of nucleosomes, the basic structural unit of DNA packaging, and a series of nucleosomes connected by linker DNAs constitute chromatins. Regulatory proteins can reorganize chromatin structures so that specific genes are transcribed in a spatiotemporal-specific manner.
DNA damage repair and transcription both require large reorganizations of nucleosomes and chromatin structures by histone modifications and chromatin remodelers, which are tightly controlled by a myriad of mechanisms in a dynamic manner. When these processes are disrupted by mutations, it can lead to diseases like cancer and neurological disorders. Our laboratory investigates how transcription factors, DNA damage response proteins, and epigenetic modifications induce changes in the structure, dynamics, and interactions of chromatin. We are also interested in studying how drugs or lead compounds bind proteins involved in these key processes. Lastly, our laboratory investigates how "liquid-liquid phase separation" can modulate transcription and DNA damage repair. To do this, we use multidisciplinary approaches, including biophysical tools (NMR and cryo-EM), molecular biology, protein chemistry, and fluorescence microscopy.
- Kim, T. H.*; Nosella, M. L.*; Bolik-Coulon, N; Harkness, R. W.; Huang S. K.; Kay, L. E.
"Correlating histone acetylation with nucleosome core particle dynamics and function." Proceedings of the National Academy of Sciences 2023, 120 (15) e2301063120. (*Both authors contributed equally).
- Kim, T. H.; Payliss, B. J.; Nosella, M. L.; Lee, I. T. W.; Toyama, Y.; Forman-Kay, J. D.; Kay, L. E.
"Interaction hot spots for phase separation revealed by NMR studies of a CAPRIN1 condensed phase" Proceedings of the National Academy of Sciences 2021 118 (23)
- Wong, L. E.*; Kim T. H.*; Muhandiram, D. R.; Forman-Kay, J. D.; Kay, L. E. (*Both authors contributed equally).
"NMR experiments for studies of dilute and condensed protein phases: Application to the phase-separating protein CAPRIN1"
Journal of the American Chemical Society. 2020, 142, 5, 2471–2489
- Kim, T. H.*; Tsang B.*; Vernon R. M.; Sonenberg N.; Kay L.E.; Forman-Kay J. D.(*Both authors contributed equally).
"Phospho-dependent phase separation of FMRP and CAPRIN1 recapitulates regulation of translation and deadenylation"
Science 2019 365 (6455), 825-829
- Mehrabi P.*; Di Pietrantonio C.*; Kim T. H.*, Sljoka A.; Taverner K.; Ing C.; Kruglyak N.; Pomès R.; Pai E. F.; Prosser R. S.(*Contributed equally to this work).
"Substrate-based Allosteric Regulation of a Homodimeric Enzyme"
Journal of the American Chemical Society 2019 141 (29), 11540−11556
- Kim, T. H.*; Mehrabi, P.*; Ren, Z; Sljoka, A; Ing, C.; Bezginov, A.; Ye L.; Pomès, R; Prosser R. S.; Pai E. F.(*Both authors contributed equally).
"The role of dimer asymmetry and protomer dynamics in enzyme catalysis"
Science 2017, 355 (6322), eaag2355
- Manglik, A.*; Kim, T. H.*; Masureel, M.; Altenbach, C.; Yang, Z.; Hilger, D.; Lerch, M. T.; Kobilka, T. S.; Thian, F. S.; Hubbell, W. L.; Prosser, R. S.; Kobilka, B. K.(*Both authors contributed equally).
"Structural insights into the dynamic process of β 2-adrenergic receptor signaling"
Cell 2015, 161, 1101
- Kim, T. H.; Chung, K. Y.; Manglik, A.; Hansen, A. L.; Dror, R. O.; Mildorf, T. J.; Shaw, D. E.; Kobilka, B. K.; Prosser, R. S.
"The role of ligands on the equilibria between functional states of a G protein-coupled receptor"
Journal of the American Chemical Society 2013 135 (25), 9465-9474
- Chung, K. Y.*; Kim, T. H.*; Manglik, A.; Alvares, R.; Kobilka, B. K.; Prosser, R. S.(*Both authors contributed equally).
"Role of detergents in conformational exchange of a G protein-coupled receptor"
Journal of Biological Chemistry 2012 287 (43), 36305-3631