Protein folding is an amazing molecular process that occurs by sorting out an astronomical number of possible conformations. In crowded cellular environment, stresses or mutations can mislead polypeptide chains to misfolded or catastrophic aggregate states. Therefore, these unnecessary proteins have to be cleared from cells for quality control and regulatory purposes. Although there have been remarkable advances in understanding these phenomena and related diseases, efforts have been largely limited to water-soluble proteins excluding the other major class of proteins that reside in cell membranes.
Our research focuses on a fundamental biological question, how membrane proteins are made and destroyed in cells. Membrane proteins comprise approximately 30% of all proteins encoded in genes and carry out numerous critical functions. The folding problem of membrane proteins is directly related to human health. Indeed, accumulation of misfolded membrane proteins causes serious diseases such as Alzheimer’s disease, cystic fibrosis, and cancer. To answer our cardinal question, we investigate two conceptually connected biological processes by biochemical and biophysical methods.
Hong, H. and Bowie J.U. Dramatic destabilization of transmembrane helix interactions by features of natural membrane environments. (2011) J. Am. Chem. Soc. 133, 11389-11398. Link to article
Hong, H., Blois, T.M., Cao, Z., and Bowie J.U. Method to measure strong protein-protein interactions in lipid bilayers using a steric trap (2010) Proc. Natl. Acad. Sci. USA 107, 19802-19807. Link to article
Blois, T.M., Hong, H., Kim, T.H. and Bowie J.U. Protein unfolding with a steric trap. (2009) J. Am. Chem. Soc. 131, 13914-13915. Link to article
Hong, H., Joh, N.H., Bowie, J.U. and Tamm, L.K. Methods for measuring the thermodynamic stability of membrane proteins. (2009) Methods in Enzymology, 455, 213-236. Link to chapter
Hong, H., Park, S., Flores, R., Reinhart, D., and Tamm, L.K. Role of aromatic side-chains in the folding and thermodynamic stability of integral membrane proteins. (2007) J. Am. Chem. Soc. 129, 8320-8327. Link to article
Hong, H., Szabo, G., and Tamm, L.K. (2006) Electrostatic couplings in OmpA ion-channel gating suggest a mechanism for pore opening. Nature Chem. Biol. 2, 627-635. Link to article
Hong, H., Patel, D.R., Tamm, L.K., and van den Berg, B. (2006) The outer membrane protein OmpW forms an eight-stranded Β-barrel with a hydrophobic channel. J. Biol. Chem. 281, 7568-7577. Cover feature. Link to article
Tamm, L.K., Hong, H., and Liang, B. (2004) Folding and assembly of Β-barrel membrane proteins. Biochim. Biophys. Acta 1666, 250-263. (Review)
Hong, H. and Tamm, L.K. Elastic coupling of integral membrane protein stability to lipid bilayer forces. (2004) Proc. Natl. Acad. Sci. USA 101, 4065-4070. Link to article