【Seminar】April 22, 2019, Monday

【Seminar】April 22, 2019, Monday

Topic: Untying a Protein Knot by Circular Permutation
Speaker: Ping-Chiang Lyu, Institute of Bioinformatics and Structural Biology, National Tsing Hua University
Date: April 22, 2019, Monday
Time: 10:30-11:30 a.m.
Venue: Teaching D Building 103 Room
Language: English

Circular permutation (CP) is a protein structural rearrangement phenomenon, through which nature allows structural homologs to have different locations of termini and thus varied activities, stabilities and functional properties. It can be applied in many fields of protein engineering. The limitation of applying CP lies in its technical complexity, high cost and uncertainty of the viability of the resulting protein variants. Not every position in a protein can be used to create a viable circular permutant, but there is still a lack of practical computational tools for evaluating the positional feasibility of CP before costly experiments are carried out. We have previously reported the CPred, the first practical method for predicting viable CP sites, to be an efficient tool for predicting viable CP cleavage sites in proteins. The knotted proteins are the family that possess a very specially folding pattern. Some of these knotted proteins play an important role in human biochemistry. How protein form knots during the folding process still an unsolved mystery. Here we report the application of our CP tool to untie the knotted proteins. We demonstrated by circular permutation the ability to rewire the sequence of a topologically knotted SPOUT RNA methyltransferase into an unknotted form. While the circular permutant adopted the same three-dimensional structure and oligomeric state as those of its knotted parent, its folding stability was markedly reduced and its ligand binding abrogated. Our findings supported the hypothesis that the universally conserved knotted topology of the SPOUT superfamily may evolve from unknotted forms through circular permutation under the selection pressure of folding robustness and more importantly functional requirements associated with the knotted structural element[1].

[1] Chuang YC, Hu IC, Lyu PC, Hsu SD. Untying a Protein Knot by Circular Permutation. J Mol Biol. 2019;431:857-63.

About the Speaker
Dr. Ping-Chiang Lyu is Professor of the Department of Medical Sciences, Adjunct Professor of the Institute of Bioinformatics and Structural Biology and Vice President and Chief of Staff of National Tsing Hua University at Hsinchu, Taiwan. His research activities primarily focus on studying the structure, function and folding of proteins. His laboratory determined the protein structure by NMR and X-ray diffraction methods. They have studied several novel proteins including, plant defesins, starch binding domain, lipid transfer protein and memory-related proteins. In the field of structural bioinformatics, his laboratory has also developed efficient search tools that can rapidly retrieve structural homologs from large protein databases and applied these tools to search the novel structural motifs, such as domain swapping and circular permutation. Currently, he is the he is the president of Taiwan Biophysical Society.



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28 March 2019