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Jae-Hyun Cho

Cho, Jae-Hyun
Jae-Hyun Cho
Assistant Professor
Office:
NMR / N113A
Email:
Phone:
979-458-5928
http://www.cho-lab.org
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.

 

Recent Publications

  1. 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.
    doi: 10.1016/j.bpj.2017.01.034. PubMed PMID:28494951. PubMed Central PMC5425357.

  2. 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.
    doi: 10.1021/acschembio.7b00168. PubMed PMID:28368102. .

  3. 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.
    doi: 10.1016/j.bbrc.2017.01.089. PubMed PMID:28111343. .

  4. 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.
    doi: 10.1016/j.bpj.2016.09.029. PubMed PMID:27806266. PubMed Central PMC5103021.

  5. 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.
    doi: 10.1016/j.bpj.2016.05.008. PubMed PMID:27332121. PubMed Central PMC4919510.

  6. 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.
    doi: 10.1073/pnas.1402054111. PubMed PMID:25099351. PubMed Central PMC4143010.

  7. 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.
    doi: 10.1021/ja409479y. PubMed PMID:24219366. PubMed Central PMC3918730.

  8. 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.
    doi: 10.1038/nsmb.2039. PubMed PMID:21532593. PubMed Central PMC3265570.

  9. 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.
    doi: 10.1021/ja909052h. PubMed PMID:20028088. PubMed Central PMC2860800.

  10. Cho, JH, Raleigh, DP. Experimental characterization of the denatured state ensemble of proteins. Methods Mol. Biol. 2009;490 :339-51.
    doi: 10.1007/978-1-59745-367-7_14. PubMed PMID:19157090. .

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