title: A Single Legionella Effector Catalyzes a Multistep Ubiquitination Pathway to Rearrange Tubular Endoplasmic Reticulum for Replication.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Kotewicz
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA; Howard Hughes Medical Institute, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA.
authors.forename: Vinay
authors.initials: V
authors.lastname: Ramabhadran
authors.affiliation: Department of Chemistry, Tufts University, 62 Talbot Ave., Medford, MA 02155, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Sjoblom
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vogel
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Haenssler
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA.
authors.forename: Mengyun
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Program in Genetics, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Behringer
authors.affiliation: Department of Chemistry, Tufts University, 62 Talbot Ave., Medford, MA 02155, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Scheck
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA; Howard Hughes Medical Institute, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA. Electronic address: ralph.isberg@tufts.edu.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Isberg
mesh_terms: D036002:ADP Ribose Transferases; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002384:Catalysis; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015321:Gene Rearrangement; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D016952:Legionella pneumophila / Q000472:pathogenicity / Q000502:physiology*; D000070798:Nogo Proteins / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D001426:Bacterial Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; D025801:Ubiquitin; D036002:ADP Ribose Transferases
keywords: ADP-ribosylation; Legionella pneumophila; Sde proteins; endoplasmic reticulum; nucleotidase; phosphodiesterase; replication vacuole formation; reticulon; transferase; type IV secretion; ubiquitin