Research focus 研究方向

Recent publications


We combined cryoEM and mass spectrometry to determine the atomic structure of a feline coronavirus spike protein.  We demonstrated the ability to directly visualize post-translationally modified glycan structures that shield most of the viral spike protein surface, which has long been a major challenge in structural biology.  In light of the resurgence of SARS, which is transmitted by coronaviruses, our technological advancement can be readily applied to examine the molecular details of infectious viral glycoproteins that are involved in host recognition and viral entry and to aid vaccine developments. This work has been published in PNAS https://www.pnas.org/content/early/2020/01/02/1908898117

“貓奴別擔心！ 冠狀病毒感染關鍵新發現 有助開發疫苗”
https://www.sinica.edu.tw/ch/news/6467


Congratulations to Manoj Kumar who demonstrated some of the very unusual characteristics of the 52 knotted human ubiquitin C-terminal hydrolases (UCHs) in withstanding the ATP-fueled mechano-unfolding-coupled proteolysis by E. coli AAA+ protease, ClpXP. This work demonstrates the stabilizing contribution of the 52 knot to the mechanostability (Sriramoju et al., BBA - Proteins and Proteomics).

SELECTED PUBLICATIONS

Folding dynamics and functions of topologically knotted proteins
  • K. T. Ko, I. C. Hu, K. F. Huang, P. C. Lyu & S.-T.D. Hsu* "Untying a knotted SPOUT RNA methyltransferase by circular permutation results in a domain-swapped dimer" (2019) Structure 27, 8:1224-33 
  • Y. C. Chuang, I. C. Hu, P. C. Lyu* & S.-T.D. Hsu* "Untying a protein knot by circular permutation" (2019) J. Mol. Biol. 431, 857-63 Featured in F1000 
  • M. K. Sriramojou, T. J. Yang & S.-T.D. Hsu* "Comparative folding analyses of unknotted versus trefoil-knotted ornithine transcarbamylases suggest stabilizing effects of protein knots" (2018) Biochem. Biophys. Res. Common. 503, 822-9
  • Y.T.C. Lee & S.-T.D. Hsu* "A natively monomeric deubiquitinase UCH-L1 forms highly dynamic but defined metastable oligomeric folding intermediates" (2018) J. Phys. Chem. Lett. 9, 2433
  • M. K. Sriramojou, Y. Chen, Y.T.C. Lee & S.-T.D. Hsu* "Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease" (2018) Sci. Rep. 8, 7076
  • I. Wang, S.Y. Chen & S.-T.D. Hsu*  "Folding analysis of the most complex Stevedore's protein knot." (2016) Sci. Rep. 6, 31514  
  • S.C. Lou, S. Wetzel, H. Zhang, E.W. Crone, Y.T. Lee, S.E. Jackson & S.-T.D. Hsu “The knotted protein UCH-L1 exhibits partially unfolded forms under native conditions that share common structural features with its kinetic folding intermediates” J. Mol. Biol. (2016) 428, 2507-20 
  • L.W. Wang, Y.N. Liu, P.C. Lyu, S.E. Jackson, S.-T.D. Hsu*. Comparative analysis of the folding dynamics and kinetics of an engineered knotted protein and its variants derived from HP0242 of Helicobacter pylori. (2015) J. Phys. Condens. Matter 27(35), 354106
  • P.M. Shih, I. Wang, Y.T. Lee, S.J. Hsieh, S.Y. Chen. L.W. Wang, C.T. Huang, C.T. Chien, C.Y. Chang & S.-T.D. Hsu “Random coil behavior of chemically denatured topologically proteins revealed by small angle X-ray scattering” J. Phys. Chem. B (2015) 119, 5437-43 
  • I. Wang, S.Y. Chen & S.-T.D. Hsu “Unraveling the folding mechanism of the smallest knotted protein, MJ0366” J. Phys. Chem. B (2015) 119, 4359-70 
G-quadruplexes 
  • Z.F. Wang, M.H. Li, W.W. Chen, S.-T.D. Hsu* & T.C. Chang* “A novel transition pathway of ligand-induced topological conversion from hybrid forms to parallel forms of human telomeric G- quadruplexes” Nucleic Acids Res., (2016) 44, 3958-68
  • M. Kuo, Z.F. Wang, T.Y. Tseng, M.H. Li, S.T.D. Hsu, J.J. Lin and T.C. Chang* "The Conformational transition of hairpin structure to G-quadruplex within the WNT1 gene promoter" J. Am. Chem. Soc. (2014) 137(1), 210-8
  • Z.F. Wang, M.H. Li, S.-T.D. Hsu, & T.C. Chang "Structural basis of sodium-potassium exchange of a human telomeric DNA quadruplex without topological conversion" Nucleic Acid Res. (2014) 42, 4723-33
  • M.H. Li, Z.F. Wang, M. Kuo, S.-T.D. Hsu*, & T.C. Chang* "Unfolding kinetics of human telomeric G-quadruplexes studied by NMR Spectroscopy" J. Phys. Chem. B. (2014) 118, 931-6
  • A. Bugaut, R. Rodriguez, S. Kumari, S.-T.D. Hsu, and S. Balasubramanian* “Small molecule-mediated inhibition of translation by targeting a native RNA G-quadruplex” Org. Biomol. Chem. (2010) 8, 2771-6
  • S.-T.D. Hsu, P. Varnai, A. Bugaut, A.P. Reszka, S. Neidle, and S. Balasubramanian “A G-rich sequence within the c-kit oncogene promoter forms a parallel G-quadruplex having asymmetric G-tetrad dynamics” J. Am. Chem. Soc. (2009) 131, 13399-409
  • Z.A.E. Waller, S.A. Sweitz, S.-T.D. Hsu and S. Balasubramanian* “A small molecule that disrupts G-quadruplex DNA and enhances gene expression” J. Am. Chem. Soc. (2009) 131, 12628-33
  • J. Dash, P.S. Shirude,S.-T.D. Hsu and S. Balasubramanian “Diarylethynyl amides that recognise the parallel conformation of genomic promoter DNA G-quadruplexes” J. Am. Chem. Soc., (2008) 130, 15950-6
Co-translational folding and chaperones 
  • L.D. Cabrita, S.-T.D. Hsu, H. Launay, C.M. Dobson* and J. Christodoulou* “Probing ribosome-nascent chain complexes produced in vivo by NMR spectroscopy” PNAS  (2009) 106, 22239-44
  • S.-T.D. Hsu, L.D. Cabrita, P. Fucini, J. Christodoulou and C.M. Dobson “Probing side-chain dynamics of a ribosome-bound nascent chain using methyl NMR spectroscopy“ J. Am. Chem. Soc. (2009) 131, 8366-7
  • S.-T.D. Hsu, C.W. Bertoncini and C.M. Dobson “The use of protonless NMR spectroscopy to alleviate the loss of information resulting from exchange-broadening“ J. Am. Chem. Soc. (2009) 131, 7222-3
  • S.-T.D. Hsu, P. Fucini, L.D. Cabrita, H. Launay, C.M. Dobson and J. Christodoulou “Structure and dynamics of a ribosome-bound nascent chain by NMR spectroscopy” PNAS (2007) 104, 16516-16521 / Must Read by F1000 
Drug discovery and biotechnology 
  • T.J. Hsieh, H.Y. Lin, Z. Tu, T.C. Lin, S.C. Wu, Y.Y. Tseng, F.T. Liu, S.-T. D. Hsu* & C.H. Lin* "Dual binding modes of thio-digalactosides with human galectins-1, -3 and -7 as the structural basis of potent and selective inhibitors” Sci. Rep., (2016) 6, 29457
  • J.H. Liao, C.T. Chien, H.Y. Wu, K.F. Huang, I. Wang, M.R. Ho, I.F. Tu, I.M. Lee, W. Li, Y.L. Shih, C.Y. Wu, P. Lukyanov, S.-T.D. Hsu* & S.H. Wu* “A multivalent marine lectin from Crenomytilus grayanus possesses anti-cancer activity through recognizing globotriose Gb3” J. Am. Chem. Soc., (2016) 138, 4787-96
  • S.-T.D. Hsu, E. Breukink, E. Tischenko, B. de Kruijff, M.A.G. Lutters, R. Kaptein, A.M.J.J. Bonvin and N.A.J. van Nuland "The nisin–lipid II complex reveals a pyrophosphate cage provides a blueprint for novel antibiotics" Nat. Struc. Mol. Biol. (2004) 11, 963-967 / Must Read by F1000 
Supported by the International Human Frontier Science Program