Faculty: Yufeng Tong, PhD
Assistant Professor, Pharmacology & Toxicology
Principal Investigator, Ubiquitin Biology, Structural Genomics Consortium
General Research Area: Ubiquitin Biology and Cell Signalling
The Ubiquitin Biology group at SGC Toronto focuses on understanding the structure, function, specificity, and enzymatic mechanism of E3 ubiquitin ligases and deubiquitinases(DUBs), including key enzymes involved in histone (de-)ubiquitylation and sumoylation. Particularly we are interested in the substrate recognition domains of Ring-inBetween-Ring type, HECT-type E3 ligases, and ubiquitin-specific proteases besides their catalytic domains. These families of proteins have been directly implicated in many human diseases like autism, cancer diabetes, leukemia, allergy, and etc. We are also interested in some guanine nucleotide exchange factors (GEFs) that share common domains ubiquitin ligases or DUBs, in particular the beta-propeller fold domains that are known to modulate protein-protein interaction.
We utilize the SGC’s established high-throughput structural biology platform for protein production, structure determination and biochemical assays to probe the function of these enzymes. We also collaborate with internal and external groups to identify small molecule compounds and biomolecules (ubiquitin variants) that will alter the activity of disease-related ligases and proteases.
Gao Y, Zhang Q, Lang Y, Liu Y, Dong X, Chen Z, Tian W, Tang J, Wu W, Tong Y, Chen Z: Human apo-SRP72 and SRP68/72 complex structures reveal the molecular basis of protein translocation. J Mol Cell Biol, 2017, DOI: 10.1093/jmcb/mjx010.
Zhang Q, Wang Z, Hou F, Harding R, Huang X, Dong A, Walker JR, Tong Y: The substrate binding domains of human SIAH E3 ubiquitin ligases are now crystal clear. BBA General Subjects, 2017, 1861:3095-3105.
Zhang Q, Harding R, Hou F, Dong A, Walker JR, Bteich J, Tong Y: Structural basis of the recruitment of ubiquitin-specific protease USP15 by spliceosome recycling factor SART3. J Biol Chem, 2016, 291:17283- 17292.
Tong Y: Developing high quality chemical probes targeting ubiquitin-specific proteases. Chin J Pharmacol Toxicol, 2016, 30:611-619
Zhang W, Wu KP, Sartori MA, Kamadurai HB, Ordureau A, Jiang C, Mercredi PY, Murchie R, Hu J, Persaud A, Mukherjee M, Li N, Doye A, Walker JR, Sheng Y, Hao Z, Li Y, Brown KR, Lemichez E, Chen J, Tong Y, Harper JW, Rotin D, Moffat J, Schulman BA, Sidhu SS: System-wide modulation of HECT E3 ligases with selective ubiquitin variant probes. Mol Cell, 2016, 62:121-136.
Zhang Q, Fan L, Hou F, Dong A, Wang YX, and Tong Y: New insights into the RNA binding and E3 ubiquitin ligase activities of Roquins. Scientific Reports, 2015, 5:15660
Fang L, Zhang L, Wei W, Jin X, Wang P, Tong Y, Li J, Du JX, Wong J: A methylation-phosphorylation switch determines Sox2 stability and function in ESC maintenance or differentiation. Mol Cell, 2014, 55:537-551.
Tong Y, Tempel W, Wang H, Yamada K, Shen L, Senisterra GA, Mackenzie F, Chishti AH, Park HW: Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin a1. Proc Natl Acad Sci USA, 2010, 107:20346-20351
Tong Y, Tempel W, Nedyalkova L, Mackenzie F, Park HW: Crystal structure of the N-acetylmannosamine kinase domain of GNE. PLoS One, 2009, 4:e7165
Tong Y, Park I, Hong BS, Nedyalkova L, Tempel W, Park HW: Crystal structure of human eIF5A1: insight into functional similarity of human eIF5A1 and eIF5A2. Proteins, 2009, 75:1040-1045
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