首頁 網站地圖 English
徐尚德 博士
副研究員
中央研究院生物化學研究所 512室
臺北市南港區115研究院路二段128號
TEL: +886-2-2785-5696 ext. 5120
FAX: +886-2-2788-9759
sthsu@gate.sinica.edu.tw
徐尚德的個人網站


Once considered the dark matter of the protein topology universe, topological knots have recently been identified in many protein structures. Despite the apparent complexity that a polypeptide chain needs to thread itself through a loop in order to form a knotted structure, emerging experimental evidence has shown that knotted proteins can unfold and refold efficiently in vitro without auxiliary factors, and that even under highly denatured conditions, the knotted structures are present. How and when these knots are formed during folding, and how they may be retained in the unfolded state remain poorly understood. Our laboratory strives to integrate biophysical and computational methods to probe the structures and dynamics of a variety of knotted proteins along their folding pathways in order to monitor knot formation and to identify potentially common key elements that are responsible for promoting the knotting events. The ability to reconstitute a de novo folding system, comprised of the target protein, the ribosome and associated chaperones, for NMR studies will also bring us closer to understating protein folding in a cellular milieu.

Reduction of complex protein backbone structures into knotted topological representation by pKnot server (http://pknot.life.nctu.edu.tw).

One of the knotted proteins, human ubiquitin C-terminal hydrolyase (UCH-L1) is associated with Parkinson’s disease. Familial mutations in UCH-L1 lead to increased aggregation propensity, a common feature in neurodegenerative diseases. Systematic biophysical and structural characterisations of the disease-associated UCH-L1 variants, including I93M, S18Y and E7A, provide better understanding at a molecular level into the underlying mechanism of the loss of function and gain of toxicity due to the familial mutations and post-translational modifications.

2000 - 2004 博士, Bijvoet生物分子研究中心, 荷蘭烏特列支大學
1998 - 2000 碩士, 生命科學系, 清華大學
1994 - 1998 學士, 物理暨生命科學系雙主修, 清華大學

2017,05 - present 副研究員, 中央研究院生物化學所
2011 - 2017,05 助研究員, 中央研究院生物化學所
2010 - 2011 助理教授, 清華大學生物資訊及結構生物研究所
2009 - 2010 研究員, 英國劍橋大學化學系
2007 - 2010 研究院士, 英國劍橋大學Wolfson學院
2006 - 2008 國際人類前鋒科學計畫(Human Frontier Science Program)長期研究員, 英國劍橋大學化學系
2005 - 2006 荷蘭皇家科學院Ramsay研究員, 英國劍橋大學化學系
2004 - 2005 初級研究員, 荷蘭烏特列支大學化學系

    論文列表
A multivalent marine lectin from Crenomytilus grayanus possesses anti-cancer activity through recognizing globotriose Gb3.
Liao JH, Chien CT, Wu HY, Huang KF, Wang I, Ho MR, Tu IF, Lee IM, Li W, Shih YL, Wu CY, Lukyanov PA, Hsu STD, Wu SH Journal of the American Chemical Society (2016)
A novel transition pathway of ligand-induced topological conversion from hybrid forms to parallel forms of human telomeric G-quadruplexes
Wang ZF, Li MH, Chen WW, Hsu STD, Chang TC NUCLEIC ACIDS RESEARCH (2016)
The knotted protein UCH-L1 exhibits partially unfolded forms under native conditions that share common structural features with its kinetic folding intermediates.
Lou SC, Wetzel S, Zhang H, Crone EW, Lee YT, Jackson SE, Hsu STD JOURNAL OF MOLECULAR BIOLOGY (2016)
Unraveling the Folding Mechanism of the Smallest Knotted Protein, MJ0366.
Wang I, Chen SY, Hsu STD JOURNAL OF PHYSICAL CHEMISTRY B (2015)
Structural basis of sodium-potassium exchange of a human telomeric DNA quadruplex without topological conversion.
Wang ZF, Li MH, Hsu STD, Chang TC Nucleic acids research (2014)
A G-rich sequence within the c-kit oncogene promoter forms a parallel G-quadruplex having asymmetric G-tetrad dynamics.
Hsu STD, Varnai P, Bugaut A, Reszka AP, Neidle S, Balasubramanian S Journal of the American Chemical Society (2009)
Probing side-chain dynamics of a ribosome-bound nascent chain using methyl NMR spectroscopy.
Hsu STD, Cabrita LD, Fucini P, Christodoulou J, Dobson CM Journal of the American Chemical Society (2009)
Use of protonless NMR spectroscopy to alleviate the loss of information resulting from exchange-broadening.
Hsu STD, Bertoncini CW, Dobson CM Journal of the American Chemical Society (2009)
Structure and dynamics of a ribosome-bound nascent chain by NMR spectroscopy.
Hsu STD, Fucini P, Cabrita LD, Launay H, Dobson CM, Christodoulou J Proceedings of the National Academy of Sciences of the United States of America (2007)
The nisin-lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics.
Hsu STD, Breukink E, Tischenko E, Lutters MA, de Kruijff B, Kaptein R, Bonvin AM, van Nuland NA Nature structural & molecular biology (2004)

Updated 2015.10.19

本站最佳解析度為 1024*768 ;本站適用瀏覽器為 IE 8.0、Firefox 10.0 以上

台北市南港區115研究院路二段128號 電話 : 02-27855696 傳真 : 02-27889759

Copyright © 2013.01 IBC, Academia Sinica. All rights reserved.    使用規範