title: Phosphoribosylation of Ubiquitin Promotes Serine Ubiquitination and Impairs Conventional Ubiquitination.
abstract: Conventional ubiquitination involves the ATP-dependent formation of amide bonds between the ubiquitin C terminus and primary amines in substrate proteins. Recently, SdeA, an effector protein of pathogenic Legionella pneumophila, was shown to mediate NAD-dependent and ATP-independent ubiquitin transfer to host proteins. Here, we identify a phosphodiesterase domain in SdeA that efficiently catalyzes phosphoribosylation of ubiquitin on a specific arginine via an ADP-ribose-ubiquitin intermediate. SdeA also catalyzes a chemically and structurally distinct type of substrate ubiquitination by conjugating phosphoribosylated ubiquitin to serine residues of protein substrates via a phosphodiester bond. Furthermore, phosphoribosylation of ubiquitin prevents activation of E1 and E2 enzymes of the conventional ubiquitination cascade, thereby impairing numerous cellular processes including mitophagy, TNF signaling, and proteasomal degradation. We propose that phosphoribosylation of ubiquitin potently modulates ubiquitin functions in mammalian cells.
authors.affiliation: Institute of Biochemistry II, School of Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany; Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany.
authors.forename: Sagar
authors.initials: S
authors.lastname: Bhogaraju
authors.affiliation: Institute of Biochemistry II, School of Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany; Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany.
authors.forename: Sissy
authors.initials: S
authors.lastname: Kalayil
authors.affiliation: Institute of Biochemistry II, School of Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany; Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany.
authors.forename: Yaobin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Biochemistry II, School of Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Bonn
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931 Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Colby
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931 Cologne, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Matic
authors.affiliation: Institute of Biochemistry II, School of Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany; Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany; Department of Immunology and Medical Genetics, University of Split, School of Medicine, Soltanska 2, 21000 Split, Croatia. Electronic address: ivan.dikic@biochem2.de.
authors.forename: Ivan
authors.initials: I
authors.lastname: Dikic
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D001426:Bacterial Proteins; D045643:DNA Repair Enzymes; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D016952:Legionella pneumophila / Q000502:physiology*; D007877:Legionnaires' Disease / Q000378:metabolism / Q000382:microbiology*; D008565:Membrane Proteins / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011755:Pyrophosphatases / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D012694:Serine / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; C503174:SdeA protein, Legionella pneumophila; D025801:Ubiquitin; C003130:phosphoribosyladenosine triphosphate; D012694:Serine; D000255:Adenosine Triphosphate; D010744:Phosphoric Monoester Hydrolases; D010727:Phosphoric Diester Hydrolases; D046988:Proteasome Endopeptidase Complex; D011755:Pyrophosphatases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes