Leave a comment

Research Interests


Proteins are versatile macromolecules that have critical functions in all biological processes. Protein structure plays a key role in its function. Moreover, proteins are not static; their conformation is dynamically changing. Therefore, we believe that “Protein function is determined by the structure and conformational dynamics of the protein.”


<Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS)>

While x-ray crystallography and NMR spectroscopy are standard techniques for obtaining high-resolution protein structures, both have limitations. One major limitation of crystallography is the crystallization process. Some proteins such as membrane proteins that have large hydrophobic regions are not suitable for crystallization. Moreover, x-ray crystallography provides structural information of only static states of proteins, and the environment of crystallization is often not physiological.

Exchange of protons between a protein and the surrounding aqueous solvent occurs as a spontaneous chemical process. The various exchange rates depend on the diversity of local environments of individual amide hydrogens. Amide hydrogens exposed to solvent will readily exchange with hydrogen in water, while those excluded from solvent are less likely to exchange protons. Thus, the exchange rate of protons provides information on the structural properties of a folded protein and contact sites between two proteins. HDX-MS adopts this phenomenon. HDX-MS has been used to track structural changes of proteins and the interface between two proteins.

A general procedure for HDX-MS can be divided into four steps: 1) deuterium on-exchange; 2) denaturation and fragmentation; 3) mass spectrometry; and 4) peptide identification and mapping. On-exchange of deuterium is performed under physiological conditions in D2O buffer. The effects of complex formation are probed during this step since the region of interface would be blocked from deuterium exchange.

Our lab uses HDX-MS to study protein structure, protein-small molecule interactions, protein-DNA interactions, protein conformational change, and protein folding. We are specifically interested in understanding conformational dynamics of membrane proteins such as GPCRs, various ion channels, and transporters.


<G Protein-Coupled Receptors (GPCRs)>

In 2012, Brian K Kobilka and Robert J Lefkowitz won the Nobel Prize in Chemistry for “studies of G-protein-coupled receptors (GPCRs)”. Dr. Chung has participated in those project while she was working as a postdoc in the Kobilka lab.  GPCRs are plasma membrane receptors that perform vital signaling functions in vision, olfactory perception, metabolism, endocrine system, neuromuscular regulation and CNS system.  Approximately 800 GPCRs are identified in the human genome, and many are involved in diseases such as cardiovascular, metabolic, neurodegenerative, psychiatric, cancer, and infectious diseases.  Thus, 40% of drugs in current use targets GPCRs for the treatment of various diseases including heart failure (e.g β-adrenoceptors), peptic ulcer (histamine receptors), prostatic carcinoma (gonadorelin receptors), hypertension (adrenergic and angiogensin receptors), pain (opioid receptors) and bronchial asthma (β2-adrenoceptors). All GPCRs share a seven-transmembrane (TM) α-helical structure with an extracelllar N-terminus and an intracellular C-terminus. Upon agonist binding on the extracellular side of GPCRs, TM segments and intracellular side of the receptor undergo conformational changes, which induce the coupling and activation of the heterotrimeric G proteins.

Our lab is studying the structural and functional mechanisms of GPCR and downstream signaling molecules.