Crystal Structures of Coronaviruses

With the recent appearance of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), coronaviruses are once again in the news. These viruses are found worldwide and some of them can create serious illness in humans. SARS (severe acute respiratory syndrome), which is caused by a coronavirus, killed hundreds of people in 2002-2003.

Assistant Professor Fang Li, an MSI Principal Investigator from the Department of Pharmacology in the Medical School, uses structural biology to study diseases including viral infections. This research investigates the structural basis for the receptor recognition mechanisms of viruses. This includes studying the structures and functions of the receptor-binding proteins found on the surfaces of viruses, as well as how they interact with host receptors. These structural studies will allow researchers to develop therapy strategies to fight virus-caused diseases.

Recently, Professor Li and his colleagues determined the crystal structure of the spike protein N-terminal domains (NTDs) of bovine coronavirus (BCoV). This finding was published in the Journal of Biological Chemistry in December 2012 (“Crystal Structure of Bovine Coronavirus Spike Protein Lectin Domain,” GQ Peng, LQ Xu, YL Lin, L Chen, JR Pasquarella, KV Holmes, F Li, Journal of Biological Chemistry, 287:41931, DOI: 10.1074/jbc.M112.418210 (2012)). The research studied the differences in the structure of the NTDs of BCoV and another coronavirus, mouse hepatitis coronavirus (MHC). While both NTDs include a human galactose-binding lectin (galectin) in their NTD structures, the former binds to sugar and the latter to a protein, CEACAM1. The Li group’s studies of the crystal structure of the NTDs show subtle differences in the receptor-binding loops. These results indicate a possible evolution path where a coronavirus incorporated this galectin into its spike proteins, which was altered as the different modern coronaviruses evolved. The researchers used the BSCL for this research.

The Li group has also published additional papers related to their research using MSI. These include:

  •  “Structural basis for multifunctional roles of mammalian aminopeptidase N,” L Chen, YL Lin, GQ Peng, F Li, Proceedings of the National Academy of Sciences of the United States of America, 109:17966, DOI: 10.1073/pnas.1210123109 (2012) 
  •  “Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus,” KL Wu, GQ Peng, M Wilken, RJ Geraghty, F Li, Journal of Biological Chemistry, 287:8904, DOI: 10.1074/jbc.M111.325803 (2012) 


Image description: A. Overall structure of BCoV NTD. Two β-sheets of NTD core are colored green and magenta, respectively, and other parts of the NTD are color cyan. N*, N terminus; C*, C terminus. The β-sandwich core structure is indicated as “core.” The two potential sugar-binding pockets above and underneath the core structure are indicated as top and bottom, respectively. B. 2Fo – Fo electron density of a portion of BCoV NTD at 1.5σ. This region includes three of the critical sugar-binding residues. (Peng G et al., “Crystal Structure of Bovine Coronavirus Spike Protein Lectin Domain,” J. Biol. Chem., 287:41931 (2012); ©2012 by the American Society for Biochemistry and Molecular Biology.)

posted on July 17, 2013

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