Dr. Syed Saif Hasan
University of Maryland School of Medicine
Department of Biochemistry and Molecular Biology
Friday, September 9, 2022
Room 120-Meyerhoff Chemistry Building
Host: Dr. Deepak Koirala
“Structural forces shaping the evolution of intra-cellular trafficking of SARS-CoV-2 spike”
The coronavirus spike tail mimics host dibasic motifs to hijack cellular coatomer for trafficking from Golgi to the viral assembly site in ER and ER-Golgi Intermediate Compartment (ERGIC). We show that the SARS-CoV-2 spike C-terminus outside the dibasic motif, exploits a lack mimicry of acidic residues in cognate host protein positions to function as the primary determinant of coatomer release. A spike Thr1273Glu C-terminal mutant that enhances host mimicry increases coatomer binding, effectively preventing the release required during infection. In cellular assays, this mutation greatly reduces spike transport and processing in the exocytic pathway, and effectively prevents spike incorporation into progeny particles. This unconventional regulation of coatomer release is mapped by crystallography to a newly generated interface in the mutant spike tail. These data point to a function of the coatomer in discriminating between newly synthesized and retrograde-retrieved spikes in ER/ERGIC for selective incorporation of the latter into progeny virions.