Coronaviruses are a large group of viruses that can cause illness in humans, other mammals, and birds. They use cell surface receptors to attach themselves to host cells. While most of them are not dangerous, causing minor illnesses such as colds, the group includes such deadly diseases as SARS and MERS. One coronavirus, mouse hepatitis virus (MHV), causes a disease in mice that has a high mortality rate.
MHV attaches to mouse cells via a receptor called mCEACAM1a. It appears that mice may have evolved an alternate receptor, mCEACAM1b, that is a much poorer receptor for MHV. MSI PI Fang Li, an associate professor in the Department of Pharmacology (Medical School), and colleagues recently published research that showed a molecular mechanism of how selective pressure could have changed the receptor to make it less hospitable to MHV. The researchers determined the crystal structure of mCEACAM1b and showed the differences between it and mCEACAM1a. This study provides insight into how evolutionary pressures could have helped mouse cells resist this deadly disease.
The paper can be found in The Journal of Biological Chemistry: Guiqing Peng, Yang Yang, Joseph R. Pasquarella, Liqing Xu, Zhaohui Qian, Kathryn V. Holmes, and Fang Li. 2017. Structural and Molecular Evidence Suggesting Coronavirus-Driven Evolution of Mouse Receptor. The Journal of Biological Chemistry 292 (6): 2174–81. doi: 10.1074/jbc.M116.764266. Professor Li uses MSI for studies of the structural and molecular basis of human diseases including virus infections, cancer, and abnormal blood pressure. His work was featured on the MSI website in June 2015: Targeting Drugs to Tumors.
Image description: Structural comparisons of mCEACAM1a and mCEACA1b. A, overlay of mCEACAM1a and mCEACAM1b in domain D1. mCEACAM1a is in black, and mCEACAM1b in yellow. VBMs in mCEACAM1a and the corresponding regions in mCEACAM1b are in blue. B, overlay of mCEACAM1a and mCEACAM1b in domain D4. C, structure of mCEACAM1b showing distribution of the residues that differ between mCEACAM1a and mCEACAM1b. Regions corresponding to VBMs in mCEACAM1a are in blue. Residues that differ between mCEACAM1a and mCEACAM1b are shown as balls and sticks. D, sequence identities and r.m.s.d. between mCEACAM1a and mCEACAM1b in different regions. r.m.s.d. were calculated using Coot. (Image and description: G Peng et al., JBC 292(6): 2174-81.)
posted on March 22, 2017