Bin Liu, PhD

Assistant Professor
Transcription and Gene Regulation

Biography

Dr. Liu is an assistant professor and section leader for transcription and gene regulation at the Hormel Institute, University of Minnesota. Dr. Liu obtained his PhD in Nanyang Technological University, Singapore, where his work focused on the structural and mechanistic studies of porcine pancreatic elastase. Briefly he had obtained the crystal structures of two important intermediates (E:S complex and the first tetrahedral intermediate) in serine protease catalysis. The results enable detailed proposals for the pathway of the acylation step to be made. The mechanistic proposals may have consequences for protease inhibition, in particular for the design of high energy intermediate analogues. Dr. Liu received his first postdoctoral training at the Scripps Research Institute, where his research focused on mechanistic crystallography of the cellular respiration enzyme: cytochrome ba3 oxidase. He had determined the crystal structures of the reduced cell respiration enzyme, and discovered the structural changes of monoxide bound cytochrome ba3 oxidase upon illumination, enabling understanding the molecular mechanisms of the enzyme.

Dr. Liu received his second postdoctoral training in Prof. Thomas A. Steitz’s lab at Yale University, where his work focused on the structural study of bacterial replisome. He had determined the crystal structures of a bacterial pre-priming complex (helicase-helicase loader-primase) and a complex of DNA polymerase III alpha, Tauc subunit and a DNA substrate. The former structure provides mechanistic insight into the critical primosome assembly. The latter one suggests the first atomic model of the whole DNA replication machine, the replisome. His recent work at Yale focused on the bacterial transcription regulation. He had obtained substantial achievements. He had determined the 3.9 Å cryo-EM structure of the intact class-I transcription activation complex, which provides the molecular basis for understanding how the classic activator CAP activates transcription via the class-I recruitment mechanism; the crystal structure of a complex of RNA polymerase, a DNA translocase RapA and a DNA-RNA hybrid, which provides the structural basis of transcription reactivation by RapA and helps to support the active back-translocation model as the general transcription regulation mechanism; the crystal structure of sS–associated transcription initiation open complexes, which provides new insights into the nucleotide addition cycle of the RNA polymerase and the mechanism of sS-dependent selective gene expression under stress; and the crystal structure of RNA polymerase in complex with a general transcription factor NusG, which suggests how NusG enhances transcription elongation and RNA polymerase processivity.

Professional Employment

July 2018 – Present
Assistant Professor
The Hormel Institute, University of Minnesota
2013 – 2018
Associate Research Scientist
Yale University, USA (under Prof. Thomas A. Steitz)
2008 – 2013
Research Associate Howard Hughes Medical Institute
Yale University, USA (under Prof. Thomas A. Steitz)
2006 – 2008
Research Associate
The Scripps Research Institute, USA (under Prof. James A. Fee)

Education

2002 – 2006
Nanyang Technological University, Singapore
Ph.D. in Biological Sciences
1999 – 2002
Wuhan University, China
M.S. in Medicine
1992 – 1997
Wuhan University, China
B.A. in Medicine

Research Interests

  • Structure and mechanism of bacterial and viral infection
  • Transcription and gene regulation
  • Transcription and its regulation in pathogenic bacteria, such as Helicobacter pylori
  • Structural determination of important large cellular macromolecular complexes using cryo-electron microscopy and X-ray crystallography

We are now open for postdoctoral fellows and visiting scholars

  • Candidates with strong laboratory skills in molecular biology, biochemistry, and protein expression/purification are welcome to contact Dr. Liu. Experience in X-ray crystallography (data processing, phase determination, model-building and refinement) or cryo-electron microscopy (grid preparation and data processing) would be a plus, but not required.

Publications (*corresponding author)

  1. Dong Wang, Dmytro Kompaniiets, Yangbo Hu,Bin Liu* Editorial: Transcription and its regulation in bacteria. Frontiers in Microbiology 2023; 14:1200443
  2. Fan Bu, Dmytro Kompaniiets,Bin Liu* How to compile different types of structural visualizations in one panel. Trends in Biochemical Sciences 2023; 48(3), 303-304 (Technology of Month)
  3. Clemens Grimm*, Bin Liu*, Vanessa J. Flegler*, Jeong Joo Kim* Developing protein structure figures. Trends in Biochemical Sciences 2023; 48(3), 199-202 (Narrative)
  4. Yangbo Hu*, Bin Liu*Roles of zinc-binding domain of bacterial RNA polymerase in transcription.Trends in Biochemical Sciences 2022; 47 (8), 710-724 (Review)
  5. Gang Ye, Bin Liu*, Fang Li* Cryo-EM structure of a SARS-CoV-2 omicron spike protein ectodomain. Nature Communications 2022; 13(1): 1214
  6. Wei Shi, Wei Zhou, Ming Chen, Yang Yang, Yangbo Hu*, Bin Liu* Structural basis for activation of Swi2/Snf2 ATPase RapA by RNA polymerase. Nucleic Acids Research 2021; 49(18) 10707-10716
  7. Chang Liu*, Wei Shi, Scott T. Becker, David G. Schatz, Bin Liu*, Yang Yang* Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme. Science 2021 373(6559): 1142-1146
  8. Yang Yang*, Chang Liu*, Wei Zhou, Wei Shi, Ming Chen, Baoyue Zhang, David G. Schatz, Yangbo Hu*, Bin Liu* Structural visualization of transcription activated by a multidrug-sensing MerR family regulator. Nature Communications 2021; 12(1): 2702
  9. Wei Shi, Baoyue Zhang, Yanan Jiang, Chang Liu, Wei Zhou, Ming Chen, Yang Yang*, Yangbo Hu*, Bin Liu* Structural basis of copper-efflux regulator-dependent transcription activation. iScience 2021; 24(5): 102449
  10. Wei Shi, Wei Zhou, Baoyue Zhang, Shaojia Huang, Yanan Jiang, Abigail Schammel, Yangbo Hu*, Bin Liu* Structural basis of bacterial σ28-mediated transcription reveals roles of the RNA polymerase zinc-binding domain. EMBO J. 2020; 39(14): e104389
  11. Wei Shi, Yanan Jiang, Yibin Deng, Zigang Dong*, Bin Liu* Visualization of two architectures in class-II CAP-dependent transcription activation. PLoS Biology 2020; 18(4): e3000706

……………………………………………………Before joining the Hormel Institute…………………..………………………………

  1.  Bin Liu, Chuan Hong, Rick K. Huang, Zhiheng Yu, Thomas A. Steitz Structural basis of bacterial transcription activation. Science 2017; 358:947-951.
  2.  Bin Liu, Thomas A. Steitz Structural insights into NusG regulating transcription elongation. Nucleic Acids Res 2017; 45 (2): 968-974.
  3.  Bin Liu, Yuhong Zuo, Thomas A. Steitz Structures of E. colisS-transcription initiation complexes provide new insights into polymerase mechanism. Proc. Natl Acad. Sci., 2016; 113 (15): 4051-4056.
  4.  Bin Liu, Yuhong Zuo, Thomas A. Steitz Structural basis for transcription reactivation by RapA. Proc. Natl Acad. Sci., 2015; 112 (7): 2006-2010.
  5. Bin Liu, William K. Eliason, Thomas A. Steitz Structure of a helicase-helicase loader complex reveals insights into mechanism of bacterial primosome assembly. Nature Communications 2013; 4:2495.
  6. Bin Liu, Jinzhong Lin, Thomas A. Steitz Structure of PolIIIα-τc-DNA complex suggests an atomic model of the replisome. Structure (Cell press). 2013; 21:658-664.
  7. Bin Liu, Yang Zhang, J. Timothy Sage, Soltis S.M., Tzanko Doukov, Ying Chen, C. David Stout and James A. Fee Structural changes that occur upon photolysis of the Fe(II)a3 – CO complex in the cytochrome ba3-oxidase of Thermus thermophilus: A combined X-ray crystallographic and infrared spectral study demonstrates CO binding to CuB. Biochim Biophys Acta. Bioenergetics 2012; 1817:658-665.
  8. Bin Liu, Ying Chen, Tzanko Doukov, Michael Soltis, C. David Stout and James A. Fee Combined microspectrophotometric and crystallographic examination of chemically-reduced and X-ray radiation-reduced forms of cytochrome ba3oxidase from Thermus thermophilus Structure of the reduced form of the enzyme. Biochemistry. 2009, 48:820-826
  9. Bin Liu, V. Mitch Luna, Ying Chen, C. David Stout and James A. Fee An unexpected outcome of surface-engineering an integral membrane protein:  Improved crystallization of cytochrome ba3 from Thermus thermophilus. Acta Cryst. F 2007, 63:1029-1034.
  10. Bin Liu, Schofield CJ, Wilmouth RC. Structural analyses on intermediates in serine protease catalysis. J. Biol. Chem. 2006, 281:24024-24035
  11. Shi ML, Sundramurthy K, Bin Liu, Tan SM, Law SK & Lescar J. The crystal structure of the plexin-semaphorin-integrin domain/hybrid domain/I-EGF1 segment from the human integrin beta2 subunit at 1.8 Å resolution. J. Biol. Chem. 2005, 280:30586-3059

Primary Research Areas

 

Transcription is the first and central step of gene expression, in which the DNA template is copied into RNA by the RNA polymerase (RNAP); thus defects in transcription and its regulation can lead to a variety of severe human diseases, including cancer. However, the lack of the structures of many more key complexes has hindered the understanding of the detailed mechanisms. Our long-term goal is to provide a structural basis for understanding the mechanisms of transcription initiation, elongation and termination by the bacterial RNAP.

We shall study the transition of transcription from initiation to termination phases, the regulation of different transcription stages by various factors and the mechanisms by which RNAP translocates with nucleotide addition in bacteria, including coli and selected pathogenic bacteria, such as Helicobacter pylori. These objectives will be achieved by structural determination of the RNAP in complex with functionally associated factors and appropriate DNA or RNA substrates captured at various steps in the processes, using cryo-electron microscopy and X-ray crystallography, as well as by appropriate biochemical experiments.

The information gained from our proposed research will greatly advance the understanding of all cellular transcription processes, benefit the development of novel antibiotics, and pave the way for discovering novel therapeutic directions and targets for transcription-related diseases.

In the meantime, we also have strong interests in determining the structures of other biologically important and disease-related (including cancer-related) cellular macromolecular complexes.

 

Contact Information