Institute of Biological Chemistry, Academia Sinica

Research

Intracellular protein degradation serves multiple vital functions in all living cells. For example, selective degradation of regulatory proteins such as transcription factors and cell cycle regulators allows rapid change in their concentration within the cell, which represents an effective form of regulation. Another important function of intracellular proteolysis is to rid the cell of potentially harmful proteins that are misfolded or damaged, which may be altered due to abnormal post-translational modification or may fail to assemble properly into complexes. These aberrant proteins may form toxic aggregates within the cell and thus need to be eliminated. Impaired or dysregulated intracellular protein degradation can lead to a wide variety of disease states. Our laboratory is interested in elucidating the structural mechanism of proteins involved in three major protein degradation systems in cells: the AAA+ proteolytic machines, autophagy, and phagocytosis. We take an integrated structural biology approach combining X-ray crystallography, nuclear magnetic resonance spectroscopy (NMR), and electron microscopy (EM) single-particle structure determination methods. We hope that our work will lead to a better understanding of the action mechanisms of proteins involved in intracellular protein degradation, which may aid the design of novel therapeutic strategies for treating diseases.

Degrees and Positions Held

• 1997 – 2002   Ph.D., Molecular Biophysics, University of Texas Southwestern Medical Center at Dallas
• 1990 – 1992   M.S., Graduate Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine
• 1986 – 1990   B.S., School of Pharmacy, National Taiwan University College of Medicine

• 2023   Outstanding Research Award, National Science and Technology Council
• 2022   Investigator Award, Academia Sinica
• 2020 – present   Joint Appointment Professor, Institute of Biochemical Sciences, College of Life Science, National Taiwan University
• 2019 – present   Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 2019 – 2022   Deputy Director, Institute of Biological Chemistry, Academia Sinica
• 2017   Outstanding Teaching Award, National Taiwan University
• 2010 – 2020   Adjunct Associate Professor, Institute of Biochemical Sciences, College of Life Science, National Taiwan University
• 2009 – 2019   Associate Research Fellow (Tenured 2014), Institute of Biological Chemistry, Academia Sinica
• 2006 – 2009   Research Scientist, Pfizer Inc.
• 2002 – 2006   HHMl Associate, Howard Hughes Medical Institute

Selected Publications

A 5+1 assemble-to-activate mechanism of the Lon proteolytic machine.  
Li S, Hsieh KY, Kuo CI, Lin TC, Lee SH, Chen YR, Wang CH, Ho MR, Ting SY, Zhang K, Chang CI  
Nature Communications. (2023)

Processive cleavage of substrate at individual proteolytic active sites of the Lon protease complex.  
Li S, Hsieh KY, Kuo CI, Su SC, Huang KF, Zhang K, Chang CI  
Science Advances (2021)

Complete three-dimensional structures of the Lon protease translocating a protein substrate.  
Li S, Hsieh KY, Kuo CI, Lee SH, Pintilie GD, Zhang K, Chang CI  
Science Advances (2021)

Molecular insights into substrate recognition and discrimination by the N-terminal domain of Lon AAA+ protease.  
Tzeng SR, Tseng YC, Lin CC, Hsu CY, Huang SJ, Kuo YT, Chang CI  
eLife (2021)

Structural Basis for the Differential Regulatory Roles of the PDZ Domain in C-Terminal Processing Proteases.  
Chueh CK, Som N, Ke LC, Ho MR, Reddy M, Chang CI  
mBio (2019)

Structural basis of adaptor-mediated protein degradation by the tail-specific PDZ-protease Prc.  
Su, M.-Y., Som, N., Wu, C-Y., Su, S.-C.,Kuo, Y.-T., Ke, L.-C., Ho, M.-R., Tzeng, S.-R., Teng, C.-H., Mengin-Lecreulx, D., Reddy, M., and Chang, C.-I  
Nature Communications (2017)

Structural Basis for the Magnesium-Dependent Activation and Hexamerization of the Lon AAA+ Protease.  
Su, S.-C., Lin, C.-C., Tai, H.-C., Ho, M.-R., Chang, M., Babu, S., Liao, J.-H., Wu, S.-H, Chang, Y.-C., Lim, C., and Chang, C.-I  
Structure (2016)

Structural Insights into the Allosteric Operation of the Lon AAA+ Protease.  
Lin, C.-C., Su, S.-C., Su, M.-Y., Liang, P.-H., Fang, C.-C., Wu, S.-H., and Chang, C.-I  
Structure (2016)

Structure of yeast Ape1 and its role in autophagic vesicle formation.  
Su MY, Peng WH, Ho MR, Su SC, Chang YC, Chen GC, Chang CI  
Autophagy (2015)

Structure of tracheal cytotoxin in complex with a heterodimeric pattern-recognition receptor.  
Chang CI, Chelliah Y, Borek D, Mengin-Lecreulx D, Deisenhofer J.  
Science (2006)

Publication List