Forum 01/27/2005

“Cryo-EM Studies on the Supramolecular Design of the SARS, Feline and Murine Coronaviruses”

Ben Neuman, Ph.D. – Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA

The emergence of SARS coronavirus (SARS-CoV) indelibly changed our appreciation of coronaviruses as mundane seasonal pathogens in 2003 when an epidemic of severe, often fatal, respiratory disease emerged from China. Coronaviruses derive their name from the protruding oligomeric ~160 kDa viral spike receptor-binding and fusion glycoproteins (S).  The viral core consists of nucleoprotein (N) and the positive stranded ~30 kb genome. The viral membrane is punctuated by the viral three-pass transmembrane glycoprotein (M).  We used electron cryomicroscopy (cryo-EM) and image analysis to examine the supramolecular structure of SARS-CoV.

The viral spikes were found to be homotrimeric and were arranged in a paracrystalline lattice.  This spike lattice was in register with a lattice of nucleoprotein molecules closely adherent to the inner bilayer leaflet. The nucleoprotein lattice may provide a scaffold that guides particle assembly on ER-Golgi intermediate compartment membranes.  In this process, the matrix protein mediates interactions between the spike and nucleoprotein molecules.  These results provide the first structural picture of the spatial relationships between the spike, nucleoprotein and matrix proteins, essential for understanding the assembly pathway of SARS coronavirus.

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