Page 43 - Hormel Institute Annual Report 2021-22

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Recent Publications:
• Hu, Y.*, & Liu, B.* (2022). Roles of zinc- binding domain of bacterial RNA polymerase in transcription. Trends Biochem Sci, 47(8), 710-724. (Invited review)
• Ye, G., Liu, B.*, & Li, F.* (2022). Cryo-EM structure of a SARS-CoV-2 omicron spike protein ectodomain. Nat Commun, 13(1), 1214.
• Shi, W., Zhou, W., Chen, M., Yang, Y., Hu,
Y.*, & Liu, B.* (2021). Structural basis for activation of Swi2/Snf2 ATPase RapA by RNA polymerase. Nucleic Acids Res, 49(18), 10707-10716.
• Liu, C.*, Shi, W., Becker, S. T., Schatz, D. G., Liu, B.*, & Yang, Y.* (2021). Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme. Science, 373(6559), 1142-1146.
• Yang, Y.*, Liu, C.*, Zhou, W., Shi, W., Chen,
M., Zhang, B., Schatz, D. G., Hu, Y.*, & Liu,
B.* (2021). Structural visualization of transcription activated by a multidrug- sensing MerR family regulator. Nat Commun, 12(1), 2702.
(*Corresponding author)
Bacterial transcription cycle.
Structural and mechanistic study of transcription and its regulation in Porphyromonas gingivalis
P. gingivalis is the keystone periodontopathogen for periodontitis, the most common inflammatory disease responsible for tooth loss in adults, affecting approx- imately 50% of people over 30 years old in United States and 10-15% of adult population worldwide. In addition, multiple systemic diseases, including respira- tory, cardiovascular, and neurodegenerative diseases, have also been revealed to be highly correlated with
P. gingivalis infection. Increasingly occurred antibiotic resistance has demanded the identification of new intervention strategies. As the main antibacterial target, RNA polymerase is the ideal research direction. However, the lack of the structures of the key P. gingivalis transcription complexes has hindered
the understanding of the detailed mechanism and precluded the identification of effective antibiotics.
Our long-term goal is to provide a structural basis for understanding the specific transcription mechanism in P. gingivalis and therefore pave the way for discovering effective drugs to eliminate P. gingivalis infection and reduce the relevant diseases.
Structural and mechanistic study of macromolecular complexes in
SARS-CoV-2
The structures of COVID-19 virus RNA polymerase
in complex with duplex RNA and antiviral drugs
are significant for us to understand the specific replication/transcription mechanism of this novel coronavirus (2019-nCoV or SARS-CoV-2), characterize how antiviral drugs bind to RNA polymerase to inhibit its transcription and therefore inhibit virus replication, and discover novel effective drugs and therapeutic strategies against COVID-19 virus infection. We are also characterizing the molecular mechanisms of
how SARS-CoV-2 functions and identifying effective nanobodies or small molecules to inhibit virus by obtaining and characterizing structures of critical complexes, especially the ones with the spike protein that mediates viral entry, induces human’s neutralizing immune response, and is the basis of current mRNA vaccines, using cryo-Electron Microscopy, X-ray crystallography and relevant biochemical experiments. The potential information gained from the proposed projects will benefit public health, greatly advance the field of coronavirus, and facilitate the design of novel antiviral agents and understanding related diseases.
SARS-CoV-2 Omicron spike protein
Lab research activities:
https://www.hi.umn.edu/research/research-sections/ transcription-and-gene-regulation/
ORCID iD: https://orcid.org/0000-0002-6581-780X