Short Research Description
Structural biology of proteins involved in RNA processing and quality control, and enzymes involved in human diseases (obesity, diabetes, cancer).
Full Research Description
Please see my lab website for more detailed information about our research and laboratory.
A major focus of our current research is on proteins involved in RNA 3'-end processing. Most eukaryotic mRNA precursors must undergo cleavage and polyadenylation in their 3'-ends before they can function as mRNAs. This processing machinery contains a large number of protein factors, which form several sub-complexes (CPSF, CstF). The goal of our research is to understand the molecular basis of this important event. We will produce crystal and cryo-EM structures of the protein subunits, protein-protein complexes, and protein-RNA complexes, and carry out functional studies to assess the structural information.
Another area of our research is on enzymes that are involved in fatty acid metabolism. These include acetyl-coenzyme A carboxylase (ACC), carnitine acyltransferase, AMP-activated protein kinase (AMPK), ATP-citrate lyase (ACLY) and others. These enzymes are important targets for drug discovery against obesity, diabetes and other human diseases. The goals of our research are to produce structural information on these enzymes, by cryo-EM and crystallography, and to understand their functions at the molecular level. The structural information will also lay the foundation for drug discovery against these targets.
- Y. Sun,* Y. Zhang,* W.S. Aik, X.-C. Yang, W.F. Marzluff, T. Walz$, Z. Dominski$ & L. Tong.$ (2020). Structure of an active human histone pre-mRNA 3'-end processing machinery. Science, 367, 700-703. (*-equal first authors, $-co-corresponding authors)
- J. Wei, S. Leit, J. Kuai, E. Therrien, S. Rafi, H.J. Harwood Jr, B. DeLaBarre & L. Tong. (2019). An allosteric mechanism for potent inhibition of human ATP-citrate lyase. Nature, 568, 566-570.
- X. Jiao, S. Doamekpor, J.G. Bird, B.E. Nickels, L. Tong, R.P. Hart & M. Kiledjian. (2017). 5’ end nicotinamide adenine dinucleotide cap in human cells promotes RNA decay through DXO-mediated deNADding. Cell, 168, 1015-1027.
- S. Luo & L. Tong. (2017). Molecular mechanism for the regulation of yeast separase by securin. Nature, 542, 255-259.
- J. Wei & L. Tong. (2015). Crystal structure of the 500-kDa yeast acetyl-CoA carboxylase holoenzyme dimer. Nature, 526, 723-727.
- B.A. Webb,* F. Forouhar,* F.-E. Szu, J. Seetharaman, L. Tong$ & D.L. Barber.$ (2015). Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations. Nature, 523, 111-114. (*–equal first authors, $–co-corresponding authors)
- T.H. Tran, Y.-S. Hsiao, J. Jo, C.-Y. Chou, L.E.P. Dietrich, T. Walz & L. Tong. (2015). Structure and function of a single-chain, multi-domain long-chain acyl-CoA carboxylase. Nature, 518, 120-124.
- K. Sureka,* P.H. Choi,* M. Precit, M. Delince, D.A. Pensinger, T.N. Huynh, A.R. Jurado, Y.A. Goo, M. Sadilek, A.T. Iavarone, J.-D. Sauer, L. Tong$ & J.J. Woodward.$ (2014). The cyclic dinucleotide c-di-AMP is an allosteric regulator of metabolic enzyme function. Cell, 158, 1389-1401. (*–equal first authors, $–co-corresponding authors)
- D. Tan, W.F. Marzluff, Z. Dominski & L. Tong. (2013) Structure of histone mRNA stem-loop, human stem-loop binding protein and 3'hExo ternary complex. Science 339: 318-321.
- C.S. Huang, P. Ge, Z.H. Zhou & L. Tong (2012) An unanticipated architecture of the 750-kDa a6b6 holoenzyme of 3-methylcrotonyl-CoA carboxylase Nature 481: 219-223.
- K. Xiang, T. Nagaike,* S. Xiang,* T. Kilic, M.M. Beh, J.L. Manley & L. Tong. (2010) Crystal structure of the human symplekin-Ssu72-CTD phosphopeptide complex. Nature 467: 729-733 (*equal second authors).
- C.S. Huang,* K. Sadre-Bazzaz,* Y. Shen, B. Deng, Z.H. Zhou & L. Tong. (2010) Crystal structure of the a6b6 holoenzyme of propionyl-coenzyme A carboxylase. Nature 466: 1001-1005 (*equal first authors).
- X. Jiao, S. Xiang, C.-S. Oh, C.E. Martin, L. Tong & M. Kiledjian. (2010) Identification of a quality-control mechanism for eukaryotic mRNA 5?-end capping. Nature 467: 608-611.
- S. Xiang, A. Cooper-Morgan, X. Jiao, M. Kiledjian, J.L. Manley & L. Tong. (2009) Structure and function of the 5?->3? exoribonuclease Rat1 and its activating partner Rai1. Nature 458: 784-788.
- G.A. Amodeo, M.J. Rudolph & L. Tong. (2007) Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1 Nature 449: 492-495.
- C. Mandel, S. Kaneko, H. Zhang, D. Gebauer, V. Vethantham, J.L. Manley & L. Tong (2006) Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end processing endonuclease Nature 444: 953-956.
- Zhang H, Yang Z, Shen Y, L. Tong (2003) Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase Science299: 2064-7.
- Jogl G, L. Tong (2003) Crystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport Cell. 112: 113-22.
- Y. Xu, X. Tao, B. Shen, T. Horng, R. Medzhitov, J.L. Manley, L. Tong (2000) Structural basis for signal transduction by the Toll/interleukin-1 receptor domains Nature 408: 111-115.