Research focus 研究方向


Our research interests are primarily focused on the investigation of the structures and properties of biological molecules, especially proteins and quadruplex-forming G-rich oligonucleotides, in the context of folding dynamics and their relationship to biological evolution and disease. We are working on the folding of knotted proteins, in particular, human ubiquitin C-terminal hydrolayses (UCHs), which have one of the most complex protein knots identified to date. A variety of biophysical, biochemical and computational approaches are employed to help understand how disease-associated mutations and post-translational modifications of various proteins affect their folding properties, thereby causing disorders.

Recent publications


Our recent paper (Sriramojou et al., Sci. Rep. (2018) 8, 7076) demonstrated the unprecedented mechanostabilities of 52-knotted human ubiquitin C-terminal hydrolases (UCHs). The ClpXP-dependent proteolysis of the human proteasome-associated UCH-L5, in particular, was 10000 times slower than that of GFP, which is chemically and thermally far more stable than any of the four UCHs. This finding hinted the functional benefits of being topologically knotted, at least for UCH-L5 that needs to work in a tug of war against the proteasome to compete for the same poly-ubiquitinated substrates.


Through comparative folding analyses of unknotted versus trefoil-knotted ornithine transcarbamylases by using hydrogen-deuterium exchange mass spectrometry (HDX-MS) in conjunction with small angle X-ray scattering and intrinsic fluorescence spectroscopy, we proposed that, in addition to substrate specificity, the knotted structures in XcAOTC and BfSOTC may play an important role in stabilising the folding dynamics, particularly around the knotted structural elements. (Sriramoju, Yang & Hsu, Biochem. Biophys. Res. Commun. (2018) in press).