An Emerging Way for Bacteria to Engage with Host Cells via Protein ADP-riboxanation DOI Creative Commons
Wei Xian, Zhiheng Tang, Qinxin Zhang

et al.

Toxins, Journal Year: 2024, Volume and Issue: 16(11), P. 467 - 467

Published: Nov. 1, 2024

Post-translational modifications (PTMs) are increasingly recognized as important strategies used by bacterial pathogens to modulate host cellular functions. Protein ADP-riboxanation, a derivative of ADP-ribosylation, has recently emerged new biochemical way which interact with cells. Recent studies have revealed that this modification broad regulatory roles in processes including cell death, protein translation, and stress granule formation. Given the vast majority ADP-riboxanases still uncharacterized, review we also highlight utility advanced proteomic tools functional dissection ADP-riboxanation events during infections.

Language: Английский

A cut above: Bacterial deubiquitinases with ubiquitin clippase activity DOI
Mark Hochstrasser

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(6), P. 1048 - 1050

Published: March 1, 2025

Language: Английский

Citations

0
Structural basis for the human SENP5’s SUMO isoform discrimination DOI Creative Commons
Lucía Sánchez-Alba, Ying Li, Matthew D. Maletic

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 22, 2025

Post-translational SUMO modification is a widespread mechanism for regulating protein function within cells. In humans, SUMO-conjugated proteins are partially regulated by the deconjugating activity of six SENP family members. The proteolytic these enzymes resides conserved catalytic domain that exhibits specificity two primary isoforms: SUMO1 and SUMO2/3. SENP5, along with SENP3, nucleolar involved in ribosome biogenesis preferentially target SUMO2/3 isoforms. Here, we present crystal structures human SENP5 complex both SUMO2 These reveal minimal interface elucidate molecular basis SENP5's preference isoform. This can be attributed to basic patch surrounding Arg624 at interface. Swapping mutagenesis structural analysis demonstrate favorably oriented interact Asp63 SUMO2/3, while its interaction equivalent Glu67 less favorable. results suggest subtle differences isoforms significantly influence their deconjugation enzymes, opening new avenues exploring regulation SUMOylation various cellular processes developing therapeutic agents targeting pathways.

Language: Английский

Citations

0
Discovery of ester-linked ubiquitylation of PARP10 mono-ADP-ribosylation in cells: a dual post-translational modification on Glu/Asp side chains DOI
Daniel S. Bejan,

Rachel E. Lacoursiere,

Jonathan N. Pruneda

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 27, 2024

Abstract The prevailing view on post-translational modifications (PTMs) is that amino acid side chains in proteins are modified with a single PTM at any given time. However, growing body of work has demonstrated crosstalk between different PTMs, some occurring the same residue. Such interplay seen ADP-ribosylation and ubiquitylation, where specialized E3 ligases ubiquitylate targets for proteasomal degradation an ADP-ribosylation-dependent manner. More recently, DELTEX family was reported to catalyze ubiquitylation 3’- hydroxy group adenine-proximal ribose free NAD + ADP-ribose vitro , generating non-canonical ubiquitin ester-linked species. In this report, we show, first time, dual occurs cells mono-ADP-ribosylated (MARylated) PARP10 Glu/Asp sites form MAR ester (MARUbe). We term process m ono- A DP-ribosyl ub iquit ylation or MARUbylation. Using chemical enzymatic treatments, including newly characterized bacterial deubiquitinase esterase-specific activity, discovered MARUbylation extended K11-linked polyubiquitin chains. Finally, mechanistic studies using ubiquitin-activating enzyme inhibitors leads its degradation, providing functional role new regulating protein turnover.

Language: Английский

Citations

1
Ubiquitylation: Sword and shield in the bacterial arsenal DOI
Jonathan N. Pruneda, Felix Randow

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(18), P. 3378 - 3380

Published: Sept. 1, 2024

Language: Английский

Citations

1
Structural diversity of the CE-clan proteases in bacteria to disarm host ubiquitin defenses DOI Creative Commons
Lucía Sánchez-Alba, Helena Borràs-Gas, Ge Huang

et al.

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

1
Bacterial ligases reveal fundamental principles of polyubiquitin specificity DOI Creative Commons
Tyler G. Franklin, Peter S. Brzović, Jonathan N. Pruneda

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(24), P. 4538 - 4554.e4

Published: Dec. 1, 2023

Homologous to E6AP C terminus (HECT) E3 ubiquitin (Ub) ligases direct substrates toward distinct cellular fates dictated by the specific form of monomeric or polymeric Ub (polyUb) signal attached. How polyUb specificity is achieved has been a long-standing mystery, despite extensive study in various hosts, ranging from yeast human. The bacterial pathogens enterohemorrhagic Escherichia coli and Salmonella Typhimurium encode outlying examples "HECT-like" (bHECT) ligases, but commonalities eukaryotic HECT (eHECT) mechanism had not explored. We expanded bHECT family with human plant pathogens. Three structures primed, Ub-loaded states resolved key details entire ligation process. One structure provided rare glimpse into act ligating polyUb, yielding means rewire both eHECT ligases. Studying this evolutionarily revealed insight function virulence factors as well fundamental principles underlying HECT-type ligation.

Language: Английский

Citations

1
A family of bacterial Josephin-like deubiquitinases with an unusual cleavage mode DOI Creative Commons
Thomas Hermanns, Susanne Kolek, Matthias Uthoff

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

Abstract Many intracellular bacteria secrete deubiquitinase (DUB) effectors into eukaryotic host cells to keep the bacterial surface or enclosing vesicle membrane free of ubiquitin marks. Here, we describe a new family DUBs that is structurally related Josephins, but contains members catalyze unique destructive substrate deubiquitination. These C-terminal clippases (UCCs) cleave before diGly motif, thereby truncating modifier and leaving remnant on substrate. By comparing crystal structures substrate-bound closely conventional DUB, identified factors causing shift found them conserved in other clippases, including one highly specific for M1-linked chains. This enzyme class has great potential as tools study system, particular aspects involving branched

Language: Английский

Citations

0
A functional screen for ubiquitin regulation identifies an E3 ligase secreted by Pseudomonas aeruginosa DOI Creative Commons
Cameron G. Roberts,

Supender Kaur,

Aaron J. Ogden

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

ABSTRACT Ubiquitin signaling controls many aspects of eukaryotic biology, including targeted protein degradation and immune defense. Remarkably, invading bacterial pathogens have adapted secreted effector proteins that hijack host ubiquitination to gain control over responses. These ubiquitin-targeted effectors can exhibit, for example, E3 ligase or deubiquitinase activities, often without any sequence structural homology ubiquitin regulators. Such convergence in function poses a challenge the discovery additional virulence factors target ubiquitin. To overcome this, we developed workflow harvest natively functionally screen them regulatory activities. After benchmarking this approach on diverse activities from Salmonella Typhimurium, Enteropathogenic Escherichia coli , Shigella flexneri applied it identification cryptic activity by Pseudomonas aeruginosa . We identified an unreported P. ligase, which termed Ub 1 (PUL-1), resembles none other ligases previously established outside system. Importantly, animal model infection, PUL-1 plays important role regulating virulence. Thus, our functional carries promise expanding appreciation how regulation contributes pathogenesis.

Language: Английский

Citations

0
Insights into ubiquitinome dynamics in the host‒pathogen interplay during Francisella novicida infection DOI Creative Commons

Luyu Yang,

Yanfeng Li, Qingqing Xie

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 18, 2024

Ubiquitination functions as an important posttranslational modification for orchestrating inflammatory immune responses and cell death during pathogenic infection. The ubiquitination machinery is a major target hijacked by bacteria to promote their survival proliferation. Type I interferon (IFN-I) plays detrimental roles in host defense against Francisella novicida (F. novicida) effects of IFN-I on the proteins F. infection remain unclear. Herein, we delineate dynamic ubiquitinome alterations both wild-type (WT) interferon-alpha receptor-deficient (Ifnar

Language: Английский

Citations

0
An Emerging Way for Bacteria to Engage with Host Cells via Protein ADP-riboxanation DOI Creative Commons
Wei Xian, Zhiheng Tang, Qinxin Zhang

et al.

Toxins, Journal Year: 2024, Volume and Issue: 16(11), P. 467 - 467

Published: Nov. 1, 2024

Post-translational modifications (PTMs) are increasingly recognized as important strategies used by bacterial pathogens to modulate host cellular functions. Protein ADP-riboxanation, a derivative of ADP-ribosylation, has recently emerged new biochemical way which interact with cells. Recent studies have revealed that this modification broad regulatory roles in processes including cell death, protein translation, and stress granule formation. Given the vast majority ADP-riboxanases still uncharacterized, review we also highlight utility advanced proteomic tools functional dissection ADP-riboxanation events during infections.

Language: Английский

Citations

0