- Undergraduate Education
- B.S., Biology, Han-Yang University, South Korea 1997
- Graduate Education
- M.S., Protein Engineering, Pohang University of Science and Technology, South Korea 1999
- Ph.D SUNY-Stonybrook 2006
- Postdoc: Columbia University
- Joined Texas A&M in 2012
Structural dynamics of multi-domain signaling proteins
The importance of understanding the regulatory mechanism of the intra-molecular interactions is highlighted by the observation that nearly 65%-80% of eukaryotic proteins consist of multiple domains. The multidomain architecture generates “emergent properties” that are not demonstrated by their individual domains and should be investigated in the context of full-length protein. In these systems, the dynamics of the intra-molecular interactions between domains provides fundamental mechanisms for many biological processes such as autoinhibition, allosteric modulation of kinase activity and molecular recognition of target proteins.
Two closely related multidomain proteins, the signaling adaptor protein Crk-II and cAbl kinase, will be targeted to delineate the underlying regulatory mechanism of intra- and inter-molecular protein-protein interactions. Dysregulation of the intramolecular interdomain interactions in Crk-II and cAbl kinase are closely associated with cancer and pathogen infection.
Our research interests lie in the interface between biology and other areas of science (chemistry and physics). NMR is our primary tool for structural and biophysical analysis. We also extensively use other techniques including Circular Dichroism and Fluorescence spectroscopy, and Isothermal calorimetry. These biophysical analyses are corroborated by sophisticated engineering and tuning of target proteins using semi-synthetic chemical biology techniques, in addition to traditional molecular biology methods.
Shen, Q, Shi, J, Zeng, D, Zhao, B, Li, P, Hwang, W et al.. Molecular Mechanisms of Tight Binding through Fuzzy Interactions. Biophys. J. 2018;114 (6):1313-1320.
Sato, S, Cho, JH, Peran, I, Soydaner-Azeloglu, RG, Raleigh, DP. The N-Terminal Domain of Ribosomal Protein L9 Folds via a Diffuse and Delocalized Transition State. Biophys. J. 2017;112 (9):1797-1806.
Shen, Q, Zeng, D, Zhao, B, Bhatt, VS, Li, P, Cho, JH et al.. The Molecular Mechanisms Underlying the Hijack of Host Proteins by the 1918 Spanish Influenza Virus. ACS Chem. Biol. 2017;12 (5):1199-1203.
Zeng, D, Shen, Q, Cho, JH. Thermodynamic contribution of backbone conformational entropy in the binding between SH3 domain and proline-rich motif. Biochem. Biophys. Res. Commun. 2017;484 (1):21-26.
Zeng, D, Bhatt, VS, Shen, Q, Cho, JH. Kinetic Insights into the Binding between the nSH3 Domain of CrkII and Proline-Rich Motifs in cAbl. Biophys. J. 2016;111 (9):1843-1853.
Bhatt, VS, Zeng, D, Krieger, I, Sacchettini, JC, Cho, JH. Binding Mechanism of the N-Terminal SH3 Domain of CrkII and Proline-Rich Motifs in cAbl. Biophys. J. 2016;110 (12):2630-2641.
Cho, JH, Meng, W, Sato, S, Kim, EY, Schindelin, H, Raleigh, DP et al.. Energetically significant networks of coupled interactions within an unfolded protein. Proc. Natl. Acad. Sci. U.S.A. 2014;111 (33):12079-84.
Stafford, KA, Ferrage, F, Cho, JH, Palmer, AG 3rd. Side chain dynamics of carboxyl and carbonyl groups in the catalytic function of Escherichia coli ribonuclease H. J. Am. Chem. Soc. 2013;135 (48):18024-7.
Cho, JH, Muralidharan, V, Vila-Perello, M, Raleigh, DP, Muir, TW, Palmer, AG 3rd et al.. Tuning protein autoinhibition by domain destabilization. Nat. Struct. Mol. Biol. 2011;18 (5):550-5.
Cho, JH, O'Connell, N, Raleigh, DP, Palmer, AG 3rd. Phi-value analysis for ultrafast folding proteins by NMR relaxation dispersion. J. Am. Chem. Soc. 2010;132 (2):450-1.