A novel polyubiquitin chain linkage formed by viral Ubiquitin resists cleavage by deubiquitinating enzymes

The project reports the structural difference between viral Ubiquitin (vUB) and human ubiquitin, hence causing local and global destabilization in vUB. Viral Ubiquitin conjugates are degraded by proteasome machinery. The in-vitro biochemical assays suggest comparable activity of mono UB and mono-vUB against different set of E2 and E3 enzymes. The project also reports the novel isopeptide linkage in viral ubiquitin at K54 position through MS/MS, which is made by E2D2 and not by other E2s used in this study. Most importantly K54-conjugates were found to be resistant towards deubiquitinase enzymes.