Assistant Professor Assistant Professor of Biochemistry, Biophysics and Structural Biology
We are interested in molecular mechanisms of membrane proteins that mediate transport of ions and molecules across lipid bilayers. Selective and regulated transport by these channels and transporters underlies many important processes in all living cells, such as import and export of nutrients and electrolytes across cell membranes, secretion of proteins and peptides, and generation of electric signals in neurons and muscle cells.
To understand how these molecular machines work, we combine structural, biochemical, and biophysical approaches. Particularly we use cryo-electron microscopy (cryo-EM) to determine atomic structures of protein complexes.
One of our research focuses is protein-conducting channels. Many proteins move across membranes to be secreted from cells or to be imported into membrane-bound organelles such as endoplasmic reticulum (ER), peroxisomes, mitochondria, and plastids. These processes are mediated by classes of membrane protein complexes called protein-conducting channels, the best example of which is the Sec61/SecY complex in eukaryotic ER or prokaryotic plasma membranes (see reviews below). In addition, protein-conducting channels mediate insertion of transmembrane proteins into a lipid bilayer and retro-translocation of damaged proteins back to the cytosol for degradation. Protein translocation poses many fundamental yet poorly understood biological questions, such as how channels selectively recognize their substrate proteins, how they translocate large polypeptides while maintaining the membrane barrier for small molecules and ions, and how they enable directional polypeptide movement. In our lab, we would like to answer these important questions by biochemical and structural analysis. We aim to visualize structures of these channels in various functional states by cryo-EM and reconstitute the translocation processes with purified components to dissect their operating principles.
Another focus of our lab lies on a group of membrane proteins called solute carriers (SLC), which mediate transport of various small molecule substrates ranging from ions to nutrients and metabolites. The SLC superfamily consists of more than 50 protein families divided based on their structure and substrates. Some SLC proteins are secondary active transporters, which couple movement of two different substrates in the same or opposite directions, whereas others are uniporters, which facilitate passive diffusion. For proteins in many SLC families, it remains unanswered how they recognize specific substrates and how their conformational changes enable substrate transport across membranes. Our goal is to elucidate their molecular mechanisms using structural and biophysical tools. As many SLC proteins are potential targets for therapeutics, they are of great biomedical importance.
Rapoport, T.A., Li, L., and Park, E. Structural and mechanistic insights into protein translocation. Annual review of cell and developmental biology (review article; published online ahead of print)
Park, E., Campbell E., MacKinnon R. (2017). Structure of a CLC-K chloride channel by cryo-electron microscopy. Nature. 541:500-505.
*Li, L., *Park, E., Ling, J., Ingram, J., Ploegh, H., and Rapoport, T.A. (2016). Crystal structure of a substrate-engaged SecY protein-translocation channel. Nature. 531:395-399.
Park, E., Ménétret, J.F., Gumbart, J.C., Ludtke, S.J., Li, W., Whynot, A., Rapoport, T.A., and Akey, C.W. (2014). Structure of the SecY channel during initiation of protein translocation. Nature. 506:102-106.
Park, E., and Rapoport, T.A. (2012). Bacterial protein translocation requires only one copy of the SecY complex in vivo. Journal of cell biology. 198:881-893.
Park, E., and Rapoport, T.A. (2012). Mechanisms of Sec61/SecY-mediated protein translocation across membranes. Annual review of biophysics. 41:21-40. (review article)
Park, E., and Rapoport, T.A. (2011). Preserving the membrane barrier for small molecules during bacterial protein translocation. Nature. 473:239-242.
*Lee, J.W., *Park, E., Jeong, M.S., Jeon, Y.J., Eom, S.H., Seol, J.H., and Chung, C.H. (2009). HslVU ATP-dependent protease utilizes maximally six among twelve threonine active sites during proteolysis. The Journal of biological chemistry. 284:33475-33484.
Ménétret, J.F., Schaletzky, J., Clemons, W.M., Jr., Osborne, A.R., Skånland, S.S., Denison, C., Gygi, S.P., Kirkpatrick, D.S., Park, E., Ludtke, S.J., Rapoport, T.A., and Akey, C.W. (2007). Ribosome binding of a single copy of the SecY complex: implications for protein translocation. Molecular cell. 28.1083-1092.
Park, E., Rho, Y.M., Koh, O.J., Ahn, S.W., Seong, I.S., Song, J.J., Bang, O., Seol, J.H., Wang, J., Eom, S.H., and Chung, C.H. (2005). Role of the GYVG pore motif of HslU ATPase in protein unfolding and translocation for degradation by HslV peptidase. The Journal of biological chemistry. 280:22892-22898.
Last Updated 2017-06-29