Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase

Gan, Ninghai; Zhen, Xiangkai; Liu, Yao; Xu, Xiaolong; He, Chunlin; Qiu, Jiazhang; Liu, Yancheng; Fujimoto, Grant M.; Nakayasu, Ernesto S.; Zhou, Biao; Zhao, Lan; Puvar, Kedar; Das, Chittaranjan; Ouyang, Songying; Luo, Zhao-Qing

doi:10.1038/s41586-019-1439-1

Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase

Journal Article · Thu Aug 15 04:00:00 EDT 2019 · Nature

DOI:https://doi.org/10.1038/s41586-019-1439-1· OSTI ID:1572484

Gan, Ninghai ^[1]; Zhen, Xiangkai ^[2]; Liu, Yao ^[1]; Xu, Xiaolong ^[2]; He, Chunlin ^[3]; Qiu, Jiazhang ^[3]; Liu, Yancheng ^[1]; Fujimoto, Grant M. ^[4]; ^[4]; Zhou, Biao ^[2]; Zhao, Lan ^[2]; Puvar, Kedar ^[1]; Das, Chittaranjan ^[1]; Ouyang, Songying ^[2]; Luo, Zhao-Qing ^[1]

Purdue University
Fujian Normal University
Jilin University
BATTELLE (PACIFIC NW LAB)

The bacterial pathogen Legionella pneumophila creates an intracellular niche permissive for its replication by extensively modulating the function of host cells using hundreds of effector proteins delivered via its Dot/Icm secretion system1. Among these, members of the SidE family (SidEs) regulate multiple cellular processes by a unique phosphoribosyl ubiquitination mechanism that bypasses the requirement of ATP and the E1, E2 enzymes of the canonical ubiquitination machinery2-4. The activity of SidEs is regulated by SidJ, another Dot/Icm effector5, but the mechanism of such regulation is not completely understood6,7. Here we demonstrate that SidJ functions to inhibit the activity of SidEs by inducing covalent attachment of a glutamate moiety to Glu860 of SdeA, which is one of the catalytic residues for the mono-ADP-ribosyltransferase activity involved in ubiquitin activation2. Furthermore, we found that the inhibition of SidEs activity by SidJ is restricted in host cells and such spatial regulation is achieved by the requirement of calmodulin (CaM), a eukaryote-specific protein, for its activity. Our results reveal a novel mechanism of regulation in bacterial virulence that features a posttranslational modification and its dependence upon a co-factor specific for host cells.

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1572484

Report Number(s):: PNNL-SA-142888

Journal Information:: Nature, Journal Name: Nature Journal Issue: 7769 Vol. 572

Country of Publication:: United States

Language:: English

References (38)

Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila Berger, Karen H.; Isberg, Ralph R. Molecular Microbiology, Vol. 7, Issue 1 https://doi.org/10.1111/j.1365-2958.1993.tb01092.x	journal	January 1993
Structural basis of substrate recognition by a bacterial deubiquitinase important for dynamics of phagosome ubiquitination Sheedlo, Michael J.; Qiu, Jiazhang; Tan, Yunhao Proceedings of the National Academy of Sciences, Vol. 112, Issue 49 https://doi.org/10.1073/pnas.1514568112	journal	November 2015
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Inhibition of Host Vacuolar H+-ATPase Activity by a Legionella pneumophila Effector Xu, Li; Shen, Xihui; Bryan, Andrew PLoS Pathogens, Vol. 6, Issue 3 https://doi.org/10.1371/journal.ppat.1000822	journal	March 2010
Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin Guo, Qing; Shen, Yuequan; Lee, Young-Sam The EMBO Journal, Vol. 24, Issue 18 https://doi.org/10.1038/sj.emboj.7600800	journal	September 2005
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Bacterial pseudokinase catalyzes protein polyglutamylation to inhibit the SidE-family ubiquitin ligases Black, Miles H.; Osinski, Adam; Gradowski, Marcin Science, Vol. 364, Issue 6442 https://doi.org/10.1126/science.aaw7446	journal	May 2019
Sequence motifs for calmodulin recognition. Rhoads, A. R.; Friedberg, F. The FASEB Journal, Vol. 11, Issue 5 https://doi.org/10.1096/fasebj.11.5.9141499	journal	April 1997
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
RNA Interference Analysis of Legionella in Drosophila Cells: Exploitation of Early Secretory Apparatus Dynamics Dorer, Marion S.; Kirton, Donald; Bader, Joel S. PLoS Pathogens, Vol. 2, Issue 4 https://doi.org/10.1371/journal.ppat.0020034	journal	January 2006
The MaxQuant computational platform for mass spectrometry-based shotgun proteomics Tyanova, Stefka; Temu, Tikira; Cox, Juergen Nature Protocols, Vol. 11, Issue 12 https://doi.org/10.1038/nprot.2016.136	journal	October 2016
The Pfam protein families database Finn, Robert D.; Mistry, Jaina; Tate, John Nucleic Acids Research, Vol. 38, Issue suppl_1 https://doi.org/10.1093/nar/gkp985	journal	November 2009
Yeast vectors for the controlled expression of heterologous proteins in different genetic backgrounds Mumberg, Dominik; Müller, Rolf; Funk, Martin Gene, Vol. 156, Issue 1 https://doi.org/10.1016/0378-1119(95)00037-7	journal	April 1995
Biological roles of cAMP: variations on a theme in the different kingdoms of life: Biological roles of cAMP Gancedo, Juana M. Biological Reviews, Vol. 88, Issue 3 https://doi.org/10.1111/brv.12020	journal	January 2013
A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination Qiu, Jiazhang; Yu, Kaiwen; Fei, Xiaowen Cell Research, Vol. 27, Issue 7 https://doi.org/10.1038/cr.2017.66	journal	May 2017
Large-scale identification of Legionella pneumophila Dot/Icm substrates that modulate host cell vesicle trafficking pathways Heidtman, Matthew; Chen, Emy J.; Moy, Man-Yu Cellular Microbiology, Vol. 11, Issue 2 https://doi.org/10.1111/j.1462-5822.2008.01249.x	journal	February 2009
Spatiotemporal Regulation of a Legionella pneumophila T4SS Substrate by the Metaeffector SidJ Jeong, Kwang Cheol; Sexton, Jessica A.; Vogel, Joseph P. PLOS Pathogens, Vol. 11, Issue 3 https://doi.org/10.1371/journal.ppat.1004695	journal	March 2015
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
Ubiquitination independent of E1 and E2 enzymes by bacterial effectors Qiu, Jiazhang; Sheedlo, Michael J.; Yu, Kaiwen Nature, Vol. 533, Issue 7601 https://doi.org/10.1038/nature17657	journal	April 2016
Insights into catalysis and function of phosphoribosyl-linked serine ubiquitination Kalayil, Sissy; Bhogaraju, Sagar; Bonn, Florian Nature, Vol. 557, Issue 7707 https://doi.org/10.1038/s41586-018-0145-8	journal	May 2018
A Single Legionella Effector Catalyzes a Multistep Ubiquitination Pathway to Rearrange Tubular Endoplasmic Reticulum for Replication Kotewicz, Kristin M.; Ramabhadran, Vinay; Sjoblom, Nicole Cell Host & Microbe, Vol. 21, Issue 2 https://doi.org/10.1016/j.chom.2016.12.007	journal	February 2017
Posttranslational glutamylation of alpha-tubulin Edde, B.; Rossier, J.; Le Caer, J. Science, Vol. 247, Issue 4938 https://doi.org/10.1126/science.1967194	journal	January 1990
Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer Luo, Z. -Q.; Isberg, R. R. Proceedings of the National Academy of Sciences, Vol. 101, Issue 3 https://doi.org/10.1073/pnas.0304916101	journal	January 2004
Fast Multi-blind Modification Search through Tandem Mass Spectrometry Na, Seungjin; Bandeira, Nuno; Paek, Eunok Molecular & Cellular Proteomics, Vol. 11, Issue 4 https://doi.org/10.1074/mcp.M111.010199	journal	December 2011
DeconMSn: a software tool for accurate parent ion monoisotopic mass determination for tandem mass spectra Mayampurath, A. M.; Jaitly, N.; Purvine, S. O. Bioinformatics, Vol. 24, Issue 7 https://doi.org/10.1093/bioinformatics/btn063	journal	February 2008
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Glutamylation Regulates Transport, Specializes Function, and Sculpts the Structure of Cilia O’Hagan, Robert; Silva, Malan; Nguyen, Ken C. Q. Current Biology, Vol. 27, Issue 22 https://doi.org/10.1016/j.cub.2017.09.066	journal	November 2017
Exploitation of the host cell ubiquitin machinery by microbial effector proteins Lin, Yi-Han; Machner, Matthias P. Journal of Cell Science, Vol. 130, Issue 12 https://doi.org/10.1242/jcs.188482	journal	May 2017
Legionella pneumophila inhibits immune signalling via MavC-mediated transglutaminase-induced ubiquitination of UBE2N Gan, Ninghai; Nakayasu, Ernesto S.; Hollenbeck, Peter J. Nature Microbiology, Vol. 4, Issue 1 https://doi.org/10.1038/s41564-018-0282-8	journal	November 2018
Post-translational regulation of ubiquitin signaling Song, Lei; Luo, Zhao-Qing The Journal of Cell Biology, Vol. 218, Issue 6 https://doi.org/10.1083/jcb.201902074	journal	April 2019
The Legionella pneumophila Effector SidJ Is Required for Efficient Recruitment of Endoplasmic Reticulum Proteins to the Bacterial Phagosome Liu, Y.; Luo, Z. -Q. Infection and Immunity, Vol. 75, Issue 2 https://doi.org/10.1128/IAI.01278-06	journal	November 2006
Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain–Ca2+/calmodulin complex Van Petegem, Filip; Chatelain, Franck C.; Minor,, Daniel L. Nature Structural & Molecular Biology, Vol. 12, Issue 12 https://doi.org/10.1038/nsmb1027	journal	November 2005
In-gel digestion for mass spectrometric characterization of proteins and proteomes Shevchenko, Andrej; Tomas, Henrik; Havli, Jan Nature Protocols, Vol. 1, Issue 6 https://doi.org/10.1038/nprot.2006.468	journal	December 2006
Enzymes Involved in AMPylation and deAMPylation Casey, Amanda K.; Orth, Kim Chemical Reviews, Vol. 118, Issue 3 https://doi.org/10.1021/acs.chemrev.7b00145	journal	August 2017
Phosphoribosylation of Ubiquitin Promotes Serine Ubiquitination and Impairs Conventional Ubiquitination Bhogaraju, Sagar; Kalayil, Sissy; Liu, Yaobin Cell, Vol. 167, Issue 6 https://doi.org/10.1016/j.cell.2016.11.019	journal	December 2016
Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin Drum, Chester L.; Yan, Shui-Zhong; Bard, Joel Nature, Vol. 415, Issue 6870 https://doi.org/10.1038/415396a	journal	January 2002
Signal-dependent DNA binding and functional domains of the quorum-sensing activator TraR as identified by repressor activity Luo, Z. -Q.; Farrand, S. K. Proceedings of the National Academy of Sciences, Vol. 96, Issue 16 https://doi.org/10.1073/pnas.96.16.9009	journal	August 1999
Legionella and Coxiella effectors: strength in diversity and activity Qiu, Jiazhang; Luo, Zhao-Qing Nature Reviews Microbiology, Vol. 15, Issue 10 https://doi.org/10.1038/nrmicro.2017.67	journal	July 2017

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