Kwang Hun Lim
Assistant Professor, 
Protein NMR Spectroscopy

Postdoctoral Fellow, UC-Berkeley, 2000-2003
PhD Chemistry, SUNY-Stony Brook, 1996-1999
MS Chemistry, POSTECH, Korea, 1993-1995  
BS Chemistry, POSTECH, Korea, 1987-1992  
     

Office: 574 Science and Technology Building
Telephone: (252) 328-9805
Fax: (252) 328-6210
E-Mail:limk@ecu.edu

Research Interests
My research interest lies in the application of NMR spectroscopy to biophysical studies of proteins, such as protein structure, dynamics, and stability. Current researches are focused on amyloidogenic proteins that are related to many types of neurodegenerative diseases, and small protein interaction modules involved in various important signal transduction pathways.

Amyloidogenic (Misfolded) Proteins
Aggregation of misfolded proteins in human body is believed to be fatal to human organism and ultimately leading to a significant number of diseases. These include various types of neurodegenerative disorders (such as transmissible spongiform encephalopathy (prion disease), Alzheimer's and Parkinson's disease), type II diabetes and amyloidosis. More than 16 different types of the proteins or polypeptides are identified to be associated with protein misfolding diseases, which are called amyloid diseases. The aggregation involves structural changes from normal celluar proteins to protein aggregates (amyloids). The aggregated proteins are insoluble, non-crystalline materials where X-ray diffraction and solution state NMR are not amenable to structural studies at the molecular level, and thus little is known about local structures at the molecular level, and the mechanism of the conformational changes is not clearly understood.

Our research interest is the application of NMR spectroscopy to comprehensive biophysical studies of amyloidogenic proteins. Solid state NMR will be used to determine three dimensional structure of the amyloids, and the conformational changes will be studied by investigating protein dynamics with the aid of multidimensional solution NMR spectroscopy. Initial studies are being performed on a small amyloidogenic PI3K SH3 domain protein, which is an excellent model system. The NMR studies will then be extended to other important amyloidogenic proteins like a-synuclein associated with Parkinson’s Disease and p53 tumor suppressor proteins that are closely related to many types of cancers.

Protein Interaction Modules in Signal Transduction Pathways
Cellular signaling processes are exquisitely regulated by protein-protein interactions that relay external stimuli to intracellular effectors, subsequently leading to a specific cellular response. A variety of protein interaction motifs that mediate the protein-protein interactions have been identified and characterized. This includes proline recognition modules, like WW and SH3 domains, and phospholylated tyrosine binding motifs, such as SH2 and PTB domains. Aberrant cell signaling processes induced by malfunction of the interaction modules have been linked to many types of diseases including cancers, diabetes and cardiovascular diseases. Knowledge of the molecular recognition properties of the protein interaction modules will, therefore, be vital to not only understanding the finely tuned signaling processes, but developing efficient therapic strategies.

Our work focuses on small protein interaction modules, WW and SH3 domains. NMR studies of the structure and dynamics on the protein-ligand complexes are currently being performed to explore molecular recognition properties of the protein binding modules, and thus protein-protein interactions.


CHEM3850_03

CHEM3850_06
CHEM1150
Presentation at ECU

Publications at ECU (* Corresponding Author)

1. K. H. Lim*,"A Weakly Clustered N-terminus Inhibits Ab Amyloidogenesis", ChemBioChem, 2006, 7, 1662-1666.

2. H. C. Ahn, Y. T. H. Le, P. S. Nagchowdhuri, E. F. DeRose, C. Putnam-Evans, R. E. London, J. L. Markley, and K. H. Lim*, "NMR Characterizations of an Amyloidogenic Conformational Ensemble of the PI3K SH3 Domain", Protein Sci., 2006, 15, 2552-2557.

3. K. H. Lim*, H. H. Collver, Y. T. Le, P. Nagchowdhuri, J. M. Kenney,"Characterizations of Distinct Amyloidogenic Conformations of the Ab (1-40) and (1-42) Peptides", Biochem. Biophys. Res. Commun., 2007, 353, 443-449.

4. K. H. Lim*, Ginger L. Henderson, Abhishek Jha, Martti Louhivuori, "Structural, Dynamic Properties of Key Residues in Ab Amyloidogenesis: Implications of an Important Role of Nanosecond Time Scale Dynamics", ChemBioChem, 2007, 8, 1251-1254.

5. K. H. Lim*, Y. K. Kim, Y. T. Chang, "Investigations of the Molecular Mechanism of Metal-Induced Ab (1-40) Amyloidogenesis", Biochemistry, 2007, 46, 13523-13532.

6. K. H. Lim* and P. Nagchowdhuri, "Non-cooperative Amyloid Formation of the PI3K SH3 Domain: Hydrophobic Collapses Implicated in Protein Folding and Misfolding", to be submitted.


Professional Service (Reviewer)

- Journal
1. Angew. Chem. Int. Ed.
2. J. Am. Chem. Soc.
3. ChemBioChem
4. Biochemistry
5. Biophys. J.
6. Chem. Phys. Lett.

- Grant
1. NSF

Publications [Ph.D. and Postdoc]

New Chem. Building Department of Chemistry
300 Science and Technology Building
East Carolina University
Greenville, NC 27858