4.4 Review

Ubiquitin-regulating effector proteins from Legionella

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Structural Basis of Ubiquitin Recognition by a Bacterial Ovarian Tumor Deubiquitinase LotA

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Summary: Pathogenic bacteria acquire eukaryotic-protein-like proteins through interaction with host cells. Bacterial effector proteins, such as LotA, mimic eukaryotic proteins and have ubiquitin ligase and deubiquitinase activities. We determined the crystal structure of LotA's middle domain and identified an essential acidic residue for its enzymatic activity.

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Substrate-assisted activation and selectivity of the bacterial RavD effector deubiquitinylase

Eric Schulze-Niemand et al.

Summary: Deubiquitinylases (DUBs) catalyze specific ubiquitin linkages cleavage at protein substrates, while effector proteins from pathogens mimic host DUB functions to avoid immune responses. RavD effector protein is functionally similar to human DUB OTULIN, both achieving selectivity through unique binding sites and substrate-assisted activation. The activation of RavD is likely substrate-assisted, contributing to its M1-substrate selectivity.

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Structural basis for protein glutamylation by the Legionella pseudokinase SidJ

Michael Adams et al.

Summary: The study reveals that Legionella pneumophila suppresses the toxicity of SdeA and other effector proteins using SidJ, and provides insights into the mechanism of protein glutamylation.

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The Activation and Selectivity of the Legionella RavD Deubiquitinase

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Serine-ubiquitination regulates Golgi morphology and the secretory pathway upon Legionella infection

Yaobin Liu et al.

Summary: The SidE family of Legionella effectors, particularly SdeA, catalyzes non-canonical phosphoribosyl-linked ubiquitination of host proteins to disrupt Golgi integrity. This disruption prevents Golgi linking proteins GRASP55 and GRASP65 from clustering and forming oligomeric structures on multiple serine residues, impacting the host secretory pathway. The Golgi manipulation strategy by Legionella highlights how the bacterium hijacks the secretory pathway to promote bacterial infection.

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Structural and mechanistic basis for protein glutamylation by the kinase fold

Adam Osinski et al.

Summary: Studies reveal that Legionella effectors SidJ and its homolog SdjA adopt a kinase fold to regulate the activity of SidE ligases through glutamylation reaction, uncovering the structural and mechanistic basis in which the kinase fold catalyzes non-ribosomal amino acid ligations.

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The Legionella Effector SdjA Is a Bifunctional Enzyme That Distinctly Regulates Phosphoribosyl Ubiquitination

Lei Song et al.

Summary: The study reveals that SdjA functions as a dual enzyme, inhibiting the activity of SdeB and SdeC by glutamylation and acting as a deglutamylase to reverse SidJ-induced glutamylation on SdeA. This dual function of SdjA highlights the unique regulation of phosphoribosyl ubiquitination by the SidJ effector family.
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Serine-linked PARP1 auto-modification controls PARP inhibitor response

Evgeniia Prokhorova et al.

Summary: Recent findings suggest that serine ADP-ribosylation plays a vital role in cellular responses to PARP1/PARP2 inhibitors. The efficient modification of three serine residues within PARP1 by HPF1 counters PARP1 trapping and contributes to inhibitor tolerance, implicating these residues as potential biomarkers for PARP inhibitor therapy.

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

Donghyuk Shin et al.

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Legionella pneumophila regulates the activity of UBE2N by deamidase-mediated deubiquitination

Ninghai Gan et al.

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Legionella effector MavC targets the Ube2N∼Ub conjugate for noncanonical ubiquitination

Kedar Puvar et al.

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Molecular Basis of Ubiquitination Catalyzed by the Bacterial Transglutaminase MavC

Guan Hongxin et al.

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Identification and characterization of diverse OTU deubiquitinases in bacteria

Alexander F. Schubert et al.

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Divergence of Legionella Effectors Reversing Conventional and Unconventional Ubiquitination

Tomoe Kitao et al.

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Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase

Ninghai Gan et al.

NATURE (2019)

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Inhibition of bacterial ubiquitin ligases by SidJ-calmodulin catalysed glutamylation

Sagar Bhogaraju et al.

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Deubiquitination of phosphoribosyl-ubiquitin conjugates by phosphodiesterase-domain-containing Legionella effectors

Min Wan et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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Structural Insights into Non-canonical Ubiquitination Catalyzed by SidE

Yong Wang et al.

Article Biochemistry & Molecular Biology

Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability

Dominika Kwasna et al.

MOLECULAR CELL (2018)

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Concise machinery for monitoring ubiquitination activities using novel artificial RING fingers

Kazuhide Miyamoto et al.

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Insights into catalysis and function of phosphoribosyl-linked serine ubiquitination

Sissy Kalayil et al.

NATURE (2018)

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Mechanism of phosphoribosyl-ubiquitination mediated by a single Legionella effector

Anil Akturk et al.

NATURE (2018)

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Structural basis of ubiquitin modification by the Legionella effector SdeA

Yanan Dong et al.

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Ubiquitination independent of E1 and E2 enzymes by bacterial effectors

Jiazhang Qiu et al.

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The increasing complexity of the ubiquitin code

Richard Yau et al.

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Structural insights into the catalysis and regulation of E3 ubiquitin ligases

Lori Buetow et al.

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Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination

Ori Braten et al.

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Molecular Characterization of LubX: Functional Divergence of the U-Box Fold by Legionella pneumophila

Andrew T. Quaile et al.

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RNF168 Promotes Noncanonical K27 Ubiquitination to Signal DNA Damage

Marco Gatti et al.

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RBR E3 ubiquitin ligases: new structures, new insights, new questions

Donald E. Spratt et al.

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Exploitation of the host ubiquitin system by human bacterial pathogens

Hiroshi Ashida et al.

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New insights into ubiquitin E3 ligase mechanism

Christopher E. Berndsen et al.

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OTULIN Antagonizes LUBAC Signaling by Specifically Hydrolyzing Met1-Linked Polyubiquitin

Kirstin Keusekotten et al.

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Status of Large-scale Analysis of Post-translational Modifications by Mass Spectrometry

Jesper V. Olsen et al.

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Smurf1-Mediated Lys29-Linked Nonproteolytic Polyubiquitination of Axin Negatively Regulates Wnt/β-Catenin Signaling

Cong Fei et al.

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Structure of a Ubiquitin E1-E2 Complex: Insights to E1-E2 Thioester Transfer

Shaun K. Olsen et al.

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Ubiquitin-Binding Proteins: Decoders of Ubiquitin-Mediated Cellular Functions

Koraljka Husnjak et al.

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Generation and physiological roles of linear ubiquitin chains

Henning Walczak et al.

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Wnt/β-Catenin Signaling and Disease

Hans Clevers et al.

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Linear ubiquitination prevents inflammation and regulates immune signalling

Bjoern Gerlach et al.

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Regulation and Cellular Roles of Ubiquitin-Specific Deubiquitinating Enzymes

Francisca E. Reyes-Turcu et al.

ANNUAL REVIEW OF BIOCHEMISTRY (2009)

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RING Domain E3 Ubiquitin Ligases

Raymond J. Deshaies et al.

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Structural basis and specificity of human otubain 1-mediated deubiquitination

Mariola J. Edelmann et al.

BIOCHEMICAL JOURNAL (2009)

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Involvement of linear polyubiquitylation of NEMO in NF-κB activation

Fuminori Tokunaga et al.

NATURE CELL BIOLOGY (2009)

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Building ubiquitin chains: E2 enzymes at work

Yihong Ye et al.

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Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways

Brenda A. Schulman et al.

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Control of AMPK-related kinases by USP9X and atypical Lys29/Lys33-inked polyubiquitin chains

Abdallah K. Al-Hakim et al.

BIOCHEMICAL JOURNAL (2008)

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Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions

Tomoko Kubori et al.

MOLECULAR MICROBIOLOGY (2008)

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Malt1 ubiquitination triggers NF-κB signaling upon T-cell activation

Andrea Oeckinghaus et al.

EMBO JOURNAL (2007)

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A ubiquitin ligase complex assembles linear polyubiquitin chains

Takayoshi Kirisako et al.

EMBO JOURNAL (2006)

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Lysine-63-linked ubiquitination is required for endolysosomal degradation of class I molecules

Lidia M. Duncan et al.

EMBO JOURNAL (2006)

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Mass spectrometric and mutational analyses reveal lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase

H Nishikawa et al.

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Structural insights into the U-box, a domain associated with multi-ubiquitination

MD Ohi et al.

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Proteomic analysis of post-translational modifications

M Mann et al.

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Legionella and Legionnaires' disease:: 25 years of investigation

BS Fields et al.

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Recognition of the polyubiquitin proteolytic signal

JS Thrower et al.

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