Yufeng Tong

Principal Investigator

University of Toronto
+1-416-946-3876

Yufeng got his Ph.D. in Molecular Biology and Biochemistry from the  Institute of Biophysics, Chinese Academy of Sciences.  He worked as a postdoc in the Case Western Reserve University to study the structure and function of the ubiquitin-like domain of plexin B1 before he joined SGC in 2006.  Yufeng is currently an Assistant Professor in the Department of Pharmacology and Toxicology at the University of Toronto and is leading the Ubiquitin Biology and Cell Signalling programs in SGC Toronto.

Research Areas

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.

Group Members

  • Qi Zhang
  • Feng Hou
Salvage or recovery of failed targets by in situ proteolysis.
Tong Y, Dong A, Xu X, Wernimont A
Methods Mol. Biol.. 2014 1140:179-88. doi: 10.1007/978-1-4939-0354-2_14
PMID: 24590718

A Strategy for Modulation of Enzymes in the Ubiquitin System.
Ernst A, Avvakumov G, Tong J, Fan Y, Zhao Y, Alberts P, Persaud A, Walker JR, Neculai AM, Neculai D, Vorobyov A, Garg P, Beatty L, Chan PK, Juang YC, Landry MC, Yeh C, Zeqiraj E, Karamboulas K, Allali-Hassani A, Vedadi M, Tyers M, Moffat J, Sicheri F, Pelletier L, Durocher D, Raught B, Rotin D, Yang J, Moran MF, Dhe-Paganon S, Sidhu SS
Science. 2013 . doi: 10.1126/science.1230161
PMID: 23287719

Crystal structure of human multiple copies in T-cell lymphoma-1 oncoprotein.
Tempel W, Dimov S, Tong Y, Park HW, Hong BS
Proteins. 2012 . doi: 10.1002/prot.24198
PMID: 23042581

Structural basis for specific binding of human MPP8 chromodomain to histone H3 methylated at lysine 9.
Li J, Li Z, Ruan J, Xu C, Tong Y, Pan PW, Tempel W, Crombet L, Min J, Zang J
PLoS ONE. 2011 6(10):e25104. doi: 10.1371/journal.pone.0025104
PMID: 22022377

Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin alpha1.
Tong Y, Tempel W, Wang H, Yamada K, Shen L, Senisterra GA, MacKenzie F, Chishti AH, Park HW
Proc. Natl. Acad. Sci. U.S.A.. 2010 107(47):20346-51. doi: 10.1073/pnas.1009008107
PMID: 21057110

Structure and function of the intracellular region of the plexin-b1 transmembrane receptor.
Tong Y, Hota PK, Penachioni JY, Hamaneh MB, Kim S, Alviani RS, Shen L, He H, Tempel W, Tamagnone L, Park HW, Buck M
J. Biol. Chem.. 2009 284(51):35962-72. doi: 10.1074/jbc.M109.056275
PMID: 19843518

2016

Characterizing Plexin GTPase Interactions Using Gel Filtration, Surface Plasmon Resonance Spectrometry, and Isothermal Titration Calorimetry.
Muller-Greven J, Kim S, Hota PK, Tong Y, Borthakur S, Buck M
Methods Mol. Biol.. 28.10.2016 1493:89-105. doi: 10.1007/978-1-4939-6448-2_6
PMID: 27787844

The substrate binding domains of human SIAH E3 ubiquitin ligases are now crystal clear.
Zhang Q, Wang Z, Hou F, Harding R, Huang X, Dong A, Walker JR, Tong Y
Biochim. Biophys. Acta. 21.10.2016 . doi: 10.1016/j.bbagen.2016.10.019
PMID: 27776223

Structural Basis of the Recruitment of Ubiquitin-Specific Protease USP15 by Spliceosome Recycling Factor SART3.
Zhang Q, Harding R, Hou F, Dong A, Walker JR, Bteich J, Tong Y
J. Biol. Chem.. 02.06.2016 . doi: 10.1074/jbc.M116.740787
PMID: 27255711

System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes.
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, Moffat J, Rotin D, Schulman BA, Sidhu SS
Mol. Cell. 02.03.2016 . doi: 10.1016/j.molcel.2016.02.005
PMID: 26949039

2015

New Insights into the RNA-Binding and E3 Ubiquitin Ligase Activities of Roquins.
Zhang Q, Fan L, Hou F, Dong A, Wang YX, Tong Y
Sci Rep. 23.10.2015 5:15660. doi: 10.1038/srep15660
PMID: 26489670

2014

A Methylation-Phosphorylation Switch Determines Sox2 Stability and Function in ESC Maintenance or Differentiation.
Fang L, Zhang L, Wei W, Jin X, Wang P, Tong Y, Li J, Du JX, Wong J
Mol. Cell. 16.07.2014 . doi: 10.1016/j.molcel.2014.06.018
PMID: 25042802

Crystal Structures of Human RNA Demethylase Alkbh5 Reveal Basis for Substrate Recognition.
Feng C, Liu Y, Wang G, Deng Z, Zhang Q, Wu W, Tong Y, Cheng C, Chen Z
J. Biol. Chem.. 10.03.2014 . doi: 10.1074/jbc.M113.546168
PMID: 24616105

Salvage or recovery of failed targets by in situ proteolysis.
Tong Y, Dong A, Xu X, Wernimont A
Methods Mol. Biol.. 05.03.2014 1140:179-88. doi: 10.1007/978-1-4939-0354-2_14
PMID: 24590718

2013

Crystal structures of malonyl-coenzyme A decarboxylase provide insights into its catalytic mechanism and disease-causing mutations.
Froese, DS; Forouhar, F; Tran, TH; Vollmar, M; Kim, YS; Lew, S; Neely, H; Seetharaman, J; Shen, Y; Xiao, R; Acton, TB; Everett, JK; Cannone, G; Puranik, S; Savitsky, P; Krojer, T; Pilka, ES; Kiyani, W; Lee, WH; Marsden, BD; von Delft, F; Allerston, CK; Spagnolo, L; Gileadi, O; Montelione, GT; Oppermann, U; Yue, WW; Tong, L;
Structure. 2.7.2013 21:1182-1192. doi: 10.1016/j.str.2013.05.001
PMID: 23791943

A Strategy for Modulation of Enzymes in the Ubiquitin System.
Ernst A, Avvakumov G, Tong J, Fan Y, Zhao Y, Alberts P, Persaud A, Walker JR, Neculai AM, Neculai D, Vorobyov A, Garg P, Beatty L, Chan PK, Juang YC, Landry MC, Yeh C, Zeqiraj E, Karamboulas K, Allali-Hassani A, Vedadi M, Tyers M, Moffat J, Sicheri F, Pelletier L, Durocher D, Raught B, Rotin D, Yang J, Moran MF, Dhe-Paganon S, Sidhu SS
Science. 03.01.2013 . doi: 10.1126/science.1230161
PMID: 23287719

2012

Crystal structure of human multiple copies in T-cell lymphoma-1 oncoprotein.
Tempel W, Dimov S, Tong Y, Park HW, Hong BS
Proteins. 08.10.2012 . doi: 10.1002/prot.24198
PMID: 23042581

IQGAP proteins reveal an atypical phosphoinositide (aPI) binding domain with a pseudo C2 domain fold.
Dixon MJ, Gray A, Schenning M, Agacan M, Tempel W, Tong Y, Nedyalkova L, Park HW, Leslie NR, van Aalten DM, Downes CP, Batty IH
J. Biol. Chem.. 29.06.2012 287(27):22483-96. doi: 10.1074/jbc.M112.352773
PMID: 22493426

Crystal structures of the tetratricopeptide repeat domains of kinesin light chains: insight into cargo recognition mechanisms.
Zhu H, Lee HY, Tong Y, Hong BS, Kim KP, Shen Y, Lim KJ, Mackenzie F, Tempel W, Park HW
PLoS ONE. 28.03.2012 7(3):e33943. doi: 10.1371/journal.pone.0033943
PMID: 22470497

2011

Target highlights in CASP9: Experimental target structures for the critical assessment of techniques for protein structure prediction.
Kryshtafovych A, Moult J, Bartual SG, Bazan JF, Berman H, Casteel DE, Christodoulou E, Everett JK, Hausmann J, Heidebrecht T, Hills T, Hui R, Hunt JF, Seetharaman J, Joachimiak A, Kennedy MA, Kim C, Lingel A, Michalska K, Montelione GT, Otero JM, Perrakis A, Pizarro JC, van Raaij MJ, Ramelot TA, Rousseau F, Tong L, Wernimont AK, Young J, Schwede T
Proteins. 21.10.2011 79 Suppl 10:6-20. doi: 10.1002/prot.23196
PMID: 22020785

Structural basis for specific binding of human MPP8 chromodomain to histone H3 methylated at lysine 9.
Li J, Li Z, Ruan J, Xu C, Tong Y, Pan PW, Tempel W, Crombet L, Min J, Zang J
PLoS ONE. 12.10.2011 6(10):e25104. doi: 10.1371/journal.pone.0025104
PMID: 22022377

Structural basis of Rnd1 binding to plexin Rho GTPase binding domains (RBDs).
Wang H, Hota PK, Tong Y, Li B, Shen L, Nedyalkova L, Borthakur S, Kim S, Tempel W, Buck M, Park HW
J. Biol. Chem.. 22.07.2011 286(29):26093-106. doi: 10.1074/jbc.M110.197053
PMID: 21610070

2010

Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin alpha1.
Tong Y, Tempel W, Wang H, Yamada K, Shen L, Senisterra GA, MacKenzie F, Chishti AH, Park HW
Proc. Natl. Acad. Sci. U.S.A.. 23.11.2010 107(47):20346-51. doi: 10.1073/pnas.1009008107
PMID: 21057110

Bardet-Biedl syndrome-associated small GTPase ARL6 (BBS3) functions at or near the ciliary gate and modulates Wnt signaling.
Wiens CJ, Tong Y, Esmail MA, Oh E, Gerdes JM, Wang J, Tempel W, Rattner JB, Katsanis N, Park HW, Leroux MR
J. Biol. Chem.. 21.05.2010 285(21):16218-30. doi: 10.1074/jbc.M109.070953
PMID: 20207729

2009

Structure and function of the intracellular region of the plexin-b1 transmembrane receptor.
Tong Y, Hota PK, Penachioni JY, Hamaneh MB, Kim S, Alviani RS, Shen L, He H, Tempel W, Tamagnone L, Park HW, Buck M
J. Biol. Chem.. 18.12.2009 284(51):35962-72. doi: 10.1074/jbc.M109.056275
PMID: 19843518

Crystal structure of the N-acetylmannosamine kinase domain of GNE.
Tong Y, Tempel W, Nedyalkova L, Mackenzie F, Park HW
PLoS ONE. 20.10.2009 4(10):e7165. doi: 10.1371/journal.pone.0007165
PMID: 19841673

Crystal structure of human eIF5A1: insight into functional similarity of human eIF5A1 and eIF5A2.
Tong Y, Park I, Hong BS, Nedyalkova L, Tempel W, Park HW
Proteins. 13.03.2009 75(4):1040-5. doi: 10.1002/prot.22378
PMID: 19280598

2008

Protein production and purification.
Gräslund S, Nordlund P, Weigelt J, Hallberg BM, Bray J, Gileadi O, Knapp S, Oppermann U, Arrowsmith C, Hui R, Ming J, dhe-Paganon S, Park HW, Savchenko A, Yee A, Edwards A, Vincentelli R, Cambillau C, Kim R, Kim SH, Rao Z, Shi Y, Terwilliger TC, Kim CY, Hung LW, Waldo GS, Peleg Y, Albeck S, Unger T, Dym O, Prilusky J, Sussman JL, Stevens RC, Lesley SA, Wilson IA, Joachimiak A, Collart F, Dementieva I, Donnelly MI, Eschenfeldt WH, Kim Y, Stols L, Wu R, Zhou M, Burley SK, Emtage JS, Sauder JM, Thompson D, Bain K, Luz J, Gheyi T, Zhang F, Atwell S, Almo SC, Bonanno JB, Fiser A, Swaminathan S, Studier FW, Chance MR, Sali A, Acton TB, Xiao R, Zhao L, Ma LC, Hunt JF, Tong L, Cunningham K, Inouye M, Anderson S, Janjua H, Shastry R, Ho CK, Wang D, Wang H, Jiang M, Montelione GT, Stuart DI, Owens RJ, Daenke S, Schütz A, Heinemann U, Yokoyama S, Büssow K, Gunsalus KC
Nat. Methods. 01.02.2008 5(2):135-46. doi: 10.1038/nmeth.f.202
PMID: 18235434

First crystallographic models of human TBC domains in the context of a family-wide structural analysis.
Tempel W, Tong Y, Dimov S, Bochkarev A, Park H
Proteins. 12.01.2008 71(1):497-502. doi: 10.1002/prot.21885
PMID: 18186464

2007

Binding of Rac1, Rnd1, and RhoD to a novel Rho GTPase interaction motif destabilizes dimerization of the plexin-B1 effector domain.
Tong Y, Chugha P, Hota PK, Alviani RS, Li M, Tempel W, Shen L, Park HW, Buck M
J. Biol. Chem.. 21.12.2007 282(51):37215-24. doi: 10.1074/jbc.M703800200
PMID: 17916560

In situ proteolysis for protein crystallization and structure determination.
Dong A, Xu X, Edwards AM, Chang C, Chruszcz M, Cuff M, Cymborowski M, Di Leo R, Egorova O, Evdokimova E, Filippova E, Gu J, Guthrie J, Ignatchenko A, Joachimiak A, Klostermann N, Kim Y, Korniyenko Y, Minor W, Que Q, Savchenko A, Skarina T, Tan K, Yakunin A, Yee A, Yim V, Zhang R, Zheng H, Akutsu M, Arrowsmith C, Avvakumov GV, Bochkarev A, Dahlgren LG, Dhe-Paganon S, Dimov S, Dombrovski L, Finerty P, Flodin S, Flores A, Gräslund S, Hammerström M, Herman MD, Hong BS, Hui R, Johansson I, Liu Y, Nilsson M, Nedyalkova L, Nordlund P, Nyman T, Min J, Ouyang H, Park HW, Qi C, Rabeh W, Shen L, Shen Y, Sukumard D, Tempel W, Tong Y, Tresagues L, Vedadi M, Walker JR, Weigelt J, Welin M, Wu H, Xiao T, Zeng H, Zhu H
Nat. Methods. 04.11.2007 4(12):1019-21. doi: 10.1038/nmeth1118
PMID: 17982461

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