Abstract
SidE family of Legionella effectors catalyze non-canonical phosphoribosyl-linked ubiquitination (PR-ubiquitination) of host proteins during bacterial infection. SdeA localizes predominantly to ER and partially to the Golgi apparatus, and mediates serine ubiquitination of multiple ER and Golgi proteins. Here we show that SdeA causes disruption of Golgi integrity due to its ubiquitin ligase activity. The Golgi linking proteins GRASP55 and GRASP65 are PR-ubiquitinated on multiple serine residues, thus preventing their ability to cluster and form oligomeric structures. In addition, we found that the functional consequence of Golgi disruption is not linked to the recruitment of Golgi membranes to the growing Legionella-containing vacuoles. Instead, it affects the host secretory pathway. Taken together, our study sheds light on the Golgi manipulation strategy by which Legionella hijacks the secretory pathway and promotes bacterial infection.
Highlights
Ubiquitination is a post-translational modification that is conserved from yeast to mammals
Unlike the conventional ubiquitination that occurs on lysine residues of substrate proteins, SidE family effectors catalyze the conjugation of Ub via a phosphoribosyl moiety to serine residues of host substrate proteins by a two-domain catalytic relay: a mono ADP-ribosyl transferase domain and a phosphodiesterase (PDE) domain [11,12,13,14]
SdeA is targeted to the ER and Golgi via its carboxyl terminus Previous structural and biochemical studies have revealed the structure of SdeA catalytic core, and the mechanism by which SdeA ubiquitinates substrates is well established [11,12,13]
Summary
Ubiquitination is a post-translational modification that is conserved from yeast to mammals. Protein ubiquitination virtually regulates every cellular processes, including protein stability, protein trafficking, immunity, and DNA repair [2,3,4,5]. Various studies have revealed that effectors of the SidE family (SdeA, SdeB, SdeC and SidE) catalyze an NAD+-dependent, ATPindependent type of ubiquitination without the need of E2 and E3 enzymes [9, 10]. Unlike the conventional ubiquitination that occurs on lysine residues of substrate proteins, SidE family effectors catalyze the conjugation of Ub via a phosphoribosyl moiety to serine residues of host substrate proteins by a two-domain catalytic relay: a mono ADP-ribosyl transferase (mART) domain and a phosphodiesterase (PDE) domain [11,12,13,14]
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