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

Just demonstrated through biophysical folding analyses that an enzyme can be loosely but surely knotted to carry out its deubiquitinase activity through entropic stabilisation "Entropic stabilization of a deubiquitinase provides conformational plasticity and slow unfolding kinetics beneficial for functioning on the proteasome" (2017) Sci. Rep. 7, 45174



Knotting of HP0242 through concatenation is the first example of an engineered protein knot. Although the crystal structure of the concatenated variant is identical to that of the parent homodimer, I showed by NMR hydroge-deuterium exchange analysis that the folding stability is reduced significantly, particularly in the region where concatenation is made, indicating that covalent linkage of protein chains do not necessarily lead to increase folding stability as intended. S.-T.D. Hsu*  "Protein knotting through concatenation significantly reduces folding stability." (2016) Sci. Rep. 6, 39357




Iren Wang et al. disentangled the folding pathway of the most complex knotted protein known to dateproviding key experimental inputs for future computational analysis "Folding analysis of the most complex Stevedore's protein knot." (2016) Sci. Rep. 6, 31514


Lou et al., "The knotted protein UCH-L1 exhibits partially unfolded forms under native conditions that share common structural features with its kinetic folding intermediates" in Journal of Molecular Biology describes the structural characteristics of a Parkinson's disease risk factor, UCH-L1 in its partially unfolded forms (PUFs) under native state and chemical denatured intermediates by NMR spectroscopy. A joint effort in collaboration with Dr Sophie Jackson at Cambridge, UK.