
Sagar Bhogaraju
Group Leader
Bhogaraju Group
EditUbiquitin signalling in bacterial pathogenicity and cancer
Group Leader
Bhogaraju Group
EditUbiquitination of proteins is involved in virtually every cellular process including protein turnover, DNA-repair, cell-cycle, vesicular transport, autophagy and innate immunity. Ubiquitination proceeds through a universally conserved process involving 3 enzyme families (E1, E2 and E3) and ATP resulting in the attachment of the C-terminal carboxyl group of ubiquitin to a lysine residue in substrate protein via an isopeptide bond. Recently, a string of exciting studies have shown that the SidE family of toxic proteins (SdeA, SdeB, SdeC & SidE) from pathogenic Legionella pneumophila can attach ubiquitin to substrates independent of E1, E2 enzymes (Qiu et al., 2016; Bhogaraju et al., 2016). My postdoctoral work has elucidated the comprehensive mechanism of SdeA-mediated ubiquitination wherein the mono-ADPribosyl transfer (mART) domain in SdeA ADPribosylates ubiquitin on Arg42. This is followed by phosphodiesterase (PDE) domain-driven cleavage of the pyrophosphate bond between α and β phosphates of ADP-ribose, linked to ubiquitin. The PDE reaction is accompanied by the attachment of ubiquitin to serines of target substrates by a phosphoribosyl linker on Arg42 (Bhogaraju et al., 2016) (Figure 1). This unique bridging of ubiquitin to substrate protein involves a phosphodiester bond instead of the canonical isopeptide bond. These studies have opened an exciting new facet of ubiquitin biology that largely remains to be explored.