Dataset Information

Mass-Spectrometric analysis of SdeA Ubiquitin modification and 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. Yet, the molecular mechanism of this ubiquitination reaction and its relevance for cellular processes remained elusive. Here, we report the identification of a phosphodiesterase (PDE) domain in SdeA that efficiently catalyses arginine phosphoribosylation of ubiquitin via an ADP-ribose intermediate . The PDE domain 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 diminishing numerous cellular processes including mitophagy, TNF signaling and proteasomal degradation. We propose that phosphoribosylation of ubiquitin is a potent modulator of ubiquitin functions in mammalian cells.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

SUBMITTER: Florian Bonn

LAB HEAD: Ivan Dikic

PROVIDER: PXD005240 | Pride | 2016-12-07

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	160630_FS1_TC_FlorianBonn_Ubiq3ATriggered.raw	Raw
	1607011_FS1_TC_FlorianBonn_Fasp_SDEA_Rab_TargettedETD.csv	Csv
	1607011_FS1_TC_FlorianBonn_Fasp_SDEA_Rab_TargettedETD.raw	Raw
	1607011_FS1_TC_FlorianBonn_Fasp_SDEA_Rab_TargettedETD.zhrs	Other
	160704_FS1_TC_FlorianBonn_Fasp_SDEA_Rab_8ul.csv	Csv

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Publications

Phosphoribosylation of Ubiquitin Promotes Serine Ubiquitination and Impairs Conventional Ubiquitination.

Bhogaraju Sagar S Kalayil Sissy S Liu Yaobin Y Bonn Florian F Colby Thomas T Matic Ivan I Dikic Ivan I

Cell 20161201 6

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. S ...[more]

PMID: 27912065

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