A Single Legionella Effector Catalyzes a Multistep Ubiquitination Pathway to Rearrange Tubular Endoplasmic Reticulum for Replication

Publication date: Available online 29 December 2016
Source:Cell Host & Microbe
Author(s): Kristin M. Kotewicz, Vinay Ramabhadran, Nicole Sjoblom, Joseph P. Vogel, Eva Haenssler, Mengyun Zhang, Jessica Behringer, Rebecca A. Scheck, Ralph R. Isberg
Intracellular pathogens manipulate host organelles to support replication within cells. For Legionella pneumophila, the bacterium translocates proteins that establish an endoplasmic reticulum (ER)-associated replication compartment. We show here that the bacterial Sde proteins target host reticulon 4 (Rtn4) to control tubular ER dynamics, resulting in tubule rearrangements as well as alterations in Rtn4 associated with the replication compartment. These rearrangements are triggered via Sde-promoted ubiquitin transfer to Rtn4, occurring almost immediately after bacterial uptake. Ubiquitin transfer requires two sequential enzymatic activities from a single Sde polypeptide: an ADP-ribosyltransferase and a nucleotidase/phosphohydrolase. The ADP-ribosylated moiety of ubiquitin is a substrate for the nucleotidase/phosphohydrolase, resulting in either transfer of ubiquitin to Rtn4 or phosphoribosylation of ubiquitin in the absence of a ubiquitination target. Therefore, a single bacterial protein drives a multistep biochemical pathway to control ubiquitination and tubular ER function independently of the host ubiquitin machinery.

Graphical abstract

Teaser

Intracellular pathogens, including Legionella, target host organelles for replication. Kotewicz et al. show that Legionella generates an ER-encompassed replication compartment via Sde protein-mediated ubiquitination of host reticulon 4. Ubiquitination is mediated by sequential action of the ADP-ribosyltransferase and nucleotidase activities of Sde and independent of the host ubiquitination system.


http://ift.tt/2iJw9h1