Regulation of Phosphoribosyl-Linked Serine Ubiquitination by Deubiquitinases DupA and DupB

Donghyuk Shin, Rukmini Mukherjee, Yaobin Liu, Alexis Gonzalez, Florian Bonn, Yan Liu, Vladimir V. Rogov, Marcel Heinz, Alexandra Stolz, Gerhard Hummer, Volker Dötsch, Zhao Qing Luo, Sagar Bhogaraju, Ivan Dikic

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24 Citations (Scopus)

Abstract

Shin et al. show that phosphoribosyl serine ubiquitination can be reversed by two deubiquitinases (DupA and DupB) from Legionella. Two DUPs specifically cleave PR-ubiquitin from serine on substrates. Catalytically inactive DupA-based proteomics approach reveals PR-ubiquitinated proteins and their roles in endoplasmic reticulum (ER) remodeling.

Original languageEnglish
Pages (from-to)164-179.e6
JournalMolecular Cell
Volume77
Issue number1
DOIs
Publication statusPublished - 2020 Jan 2

Bibliographical note

Funding Information:
We thank Mohit Misra and Marta Campus Alonso for their contribution in protein purification; Anshu Khatri and Frank Löhr for their technical assistance in NMR titration assay; Apirat Chaikuad and Stefan Knapp for advices in structure determination and sharing synchrotron time; and Sissy Kalayil, Daniella Hoeller, and Hadir Marei for discussion and critical reading of the manuscript. The authors also thank staff at SLS for their support during crystallographic X-ray diffraction test and data collection and Ulf Schwarz from Leica for STED image microscope image collection. The data collection at SLS has been supported by the funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 730872 , project CALIPSOplus. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (I.D., grant agreement No 742720 ). It was also supported by the LOEWE program DynaMem of the State of Hesse (Germany), the Alexander-von-Humboldt Foundation (to R.M.) and the German Research Foundation (DFG; Leibniz-Program to I.D.; CEF-MC - EXC115/2 ; SFB 1177 ; SFB 902 ), the Max Planck Society and by National Institutes of Health grant R01AI127465 (Z.-Q.L.).

Funding Information:
We thank Mohit Misra and Marta Campus Alonso for their contribution in protein purification; Anshu Khatri and Frank L?hr for their technical assistance in NMR titration assay; Apirat Chaikuad and Stefan Knapp for advices in structure determination and sharing synchrotron time; and Sissy Kalayil, Daniella Hoeller, and Hadir Marei for discussion and critical reading of the manuscript. The authors also thank staff at SLS for their support during crystallographic X-ray diffraction test and data collection and Ulf Schwarz from Leica for STED image microscope image collection. The data collection at SLS has been supported by the funding from the European Union's Horizon 2020 research and innovation program under grant agreement number 730872, project CALIPSOplus. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (I.D. grant agreement No 742720). It was also supported by the LOEWE program DynaMem of the State of Hesse (Germany), the Alexander-von-Humboldt Foundation (to R.M.) and the German Research Foundation (DFG; Leibniz-Program to I.D.; CEF-MC - EXC115/2; SFB 1177; SFB 902), the Max Planck Society and by National Institutes of Health grant R01AI127465 (Z.-Q.L.). D.S. R.M. and I.D. designed the conceptual framework of the study and experiments. D.S. performed crystallization, structure determination, and biochemical and biophysical characterization of DupA and contributed protein purification. R.M. and A.G. performed validation and characterization of PR-ubiquitinated substrates. R.M. contributed cellular imaging. Yaobin Liu. identified DupA/B and performed initial biochemical characterization of Dup activity and bacterial infection experiments. A.G. and F.B. contributed to identify novel PR-ubiquitinated substrates. Yan Liu created mutant strains of Legionella. V.V.R. performed NMR titration assay. F.B. performed mass spectrometry. M.H. performed MD simulation. A.S. contributed generation of FAM134 specific antibodies. G.H. V.D, Z.-Q.L. S.B. and I.D. analyzed the data. D.S. R.M. and I.D. wrote the manuscript and all authors commented on it. The authors declare no competing interests.

Publisher Copyright:
© 2019 The Authors

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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