The Shigella Type Three Secretion System Effector OspG Directly and Specifically Binds to Host Ubiquitin for Activation

The genus Shigella infects human gut epithelial cells to cause diarrhea and gastrointestinal disorders. Like many other Gram-negative bacterial pathogens, the virulence of Shigella spp. relies on a conserved type three secretion system that delivers a handful of effector proteins into host cells to manipulate various host cell physiology. However, many of the Shigella type III effectors remain functionally uncharacterized. Here we observe that OspG, one of the Shigella effectors, interacted with ubiquitin conjugates and poly-ubiquitin chains of either K48 or K63 linkage in eukaryotic host cells. Purified OspG protein formed a stable complex with ubiquitin but showed no interactions with other ubiquitin-like proteins. OspG binding to ubiquitin required the carboxyl terminal helical region in OspG and the canonical I44-centered hydrophobic surface in ubiquitin. OspG and OspG-homologous effectors, NleH1/2 from enteropathogenic E coli (EPEC), contain sub-domains I-VII of eukaryotic serine/threonine kinase. GST-tagged OspG and NleH1/2 could undergo autophosphorylation, the former of which was significantly stimulated by ubiquitin binding. Ubiquitin binding was also required for OspG functioning in attenuating host NF-κB signaling. Our data illustrate a new mechanism that bacterial pathogen like Shigella exploits ubiquitin binding to activate its secreted virulence effector for its functioning in host eukaryotic cells.

• Publication year

  2013

• Venue

  PLoS ONE

• Publication date

  2013-02-28

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0057558PMID 23469023PMCID 3585378
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Structurally distinct bacterial TBC-like GAPs link Arf GTPase to Rab1 inactivation to counteract host defenses.

  2012cited by this paper
• Ubiquitin-like proteins.

  2012cited by this paper
• The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory response

  2012cited by this paper
• The ubiquitin code.

  2012cited by this paper
• Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions.

  2012cited by this paper
• The role of ubiquitylation in immune defence and pathogen evasion

  2011cited by this paper
• The Acetyltransferase Activity of the Bacterial Toxin YopJ of Yersinia Is Activated by Eukaryotic Host Cell Inositol Hexakisphosphate

  2010cited by this paper
• NleH effectors interact with Bax inhibitor-1 to block apoptosis during enteropathogenic Escherichia coli infection

  2010cited by this paper
• Glutamine Deamidation and Dysfunction of Ubiquitin/NEDD8 Induced by a Bacterial Effector Family

  2010cited by this paper
• A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKγ to dampen the host NF-κB-mediated inflammatory response

  2010cited by this paper
• Origin and function of ubiquitin-like proteins

  2009cited by this paper
• Structural insights into host GTPase isoform selection by a family of bacterial GEF mimics

  2009cited by this paper
• Structure of the Shigella T3SS effector IpaH defines a new class of E3 ubiquitin ligases

  2008cited by this paper
• Structure of a Shigella effector reveals a new class of ubiquitin ligases

  2008cited by this paper
• The versatility of Shigella effectors

  2008cited by this paper
• Faculty Opinions recommendation of An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses.

  2007cited by this paper
• Yeast Functional Genomic Screens Lead to Identification of a Role for a Bacterial Effector in Innate Immunity Regulation

  2007cited by this paper
• The Phosphothreonine Lyase Activity of a Bacterial Type III Effector Family

  2007cited by this paper
• Type III secretion effectors of the IpaH family are E3 ubiquitin ligases.

  2007cited by this paper
• Bacterial Interference of Ubiquitination and Deubiquitination

  2007cited by this paper
• Shigella IpgB1 promotes bacterial entry through the ELMO–Dock180 machinery

  2007cited by this paper
• Shigella’s ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival?

  2007cited by this paper
• An injected bacterial effector targets chromatin access for transcription factor NF-κB to alter transcription of host genes involved in immune responses

  2007cited by this paper
• Ubiquitin-binding domains.

  2006cited by this paper
• The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes.

  2005influential reference
• Activation of a Phytopathogenic Bacterial Effector Protein by a Eukaryotic Cyclophilin

  2005cited by this paper
• Analysis of virulence plasmid gene expression defines three classes of effectors in the type III secretion system of Shigella flexneri.

  2005cited by this paper
• Ubiquitin-binding domains

  2005cited by this paper
• IpgB1 Is a Novel Shigella Effector Protein Involved in Bacterial Invasion of Host Cells

  2005cited by this paper
• Ubiquitin-Like Proteins

  2004cited by this paper
• Sequence and structure classification of kinases.

  2002cited by this paper
• A distinctive role for the Yersinia protein kinase: actin binding, kinase activation, and cytoskeleton disruption.

  2000cited by this paper
• Kinetic mechanism of the p38-alpha MAP kinase: phosphoryl transfer to synthetic peptides.

  2000cited by this paper
• The virulence plasmid pWR100 and the repertoire of proteins secreted by the type III secretion apparatus of Shigella flexneri

  2000cited by this paper
• The ubiquitin-proteasome pathway and pathogenesis of human diseases.

  1999cited by this paper
• Pathogenesis of shigellosis: from molecular and cellular biology of epithelial cell invasion to tissue inflammation and vaccine development.

  1998cited by this paper
• Pyridinyl Imidazole Inhibitors of p38 Mitogen-activated Protein Kinase Bind in the ATP Site*

  1997cited by this paper
• Three protein kinase structures define a common motif.

  1994cited by this paper
• ATPase-promoting dead end inhibitors of the cAMP-dependent protein kinase.

  1993cited by this paper
• The large virulence plasmid of Shigella.

  1992cited by this paper
• The intrinsic ATPase activity of protein kinase C is catalyzed at the active site of the enzyme.

  1992cited by this paper

• Regulation of Shigella effector kinase OspG by Musa acuminata fruit extracts: An in vitro, in vivo, and in silico study

  2026cites this paper
• Regulation of bacterial phosphorelay systems

  2025cites this paper
• Modulation of host functions by bacterial serine/threonine protein kinase effector proteins

  2025influential citation
• Molecular Mimicry by Bacterial Effector Proteins

  2025cites this paper
• E2 conjugating enzymes: A silent but crucial player in Ubiquitin Biology.

  2025cites this paper
• The multifaceted nature of SUMOylation in heart disease and its therapeutic potential

  2025cites this paper
• The Shigella kinase effector OspG modulates host ubiquitin signaling to escape septin-cage entrapment

  2024cites this paper
• Ubiquitin‐targeted bacterial effectors: rule breakers of the ubiquitin system

  2023cites this paper
• Immune evasion and persistence in enteric bacterial pathogens

  2023cites this paper
• Bacterial effector kinases and strategies to identify their target host substrates

  2023cites this paper
• A bacterial kinase phosphorylates OSK1 to suppress stomatal immunity in rice

  2021cites this paper
• Interesting Biochemistries in the Structure and Function of Bacterial Effectors

  2021influential citation
• Structural insights of macromolecules involved in bacteria-induced apoptosis in the pathogenesis of human diseases.

  2021cites this paper
• Protein Export and Secretion Among Bacterial Pathogens

  2020influential citation
• Staying out or Going in? The Interplay between Type 3 and Type 5 Secretion Systems in Adhesion and Invasion of Enterobacterial Pathogens

  2020cites this paper
• A human pathogenic bacterium Shigella proliferates in plants through adoption of type III effectors for shigellosis.

  2019cites this paper
• Visualizing ubiquitination in mammalian cells

  2019cites this paper
• Thinking outside of the cell: Secreted protein kinases in bacteria, parasites, and mammals

  2019cites this paper
• A Bacterial Effector Mimics a Host HSP90 Client to Undermine Immunity.

  2019cites this paper
• The human pathogenic bacterium Shigella proliferates in Arabidopsis 1 plants through type III effector-mediated immune suppression

  2018cites this paper
• Regulation of Shigella Effector Kinase OspG through Modulation of Its Dynamic Properties.

  2018cites this paper
• Cooperative Immune Suppression by Escherichia coli and Shigella Effector Proteins

  2018influential citation
• The Xanthomonas euvesicatoria type III effector XopAU is an active protein kinase that manipulates plant MAP kinase signaling

  2018cites this paper
• Conformational Arrangements of UbcH7-Ubiquitin with OspG and Parkin

  2018influential citation
• Human pathogenic bacterium Shigella infects Arabidopsis plants using type-III effectors that suppress conserved MAP kinase signaling

  2018cites this paper
• Exploitation of the host cell ubiquitin machinery by microbial effector proteins

  2017cites this paper
• Dissecting the signaling pathways controlling inflammation during Gram-negative bacterial infections : the role of ALPK1, TIFA and TRAF6 during Shigella flexneri infection

  2017cites this paper
• Type III Secretion in the Melioidosis Pathogen Burkholderia pseudomallei

  2017cites this paper
• [Progress on mechanisms for pathogensto evade NOD-like receptor and Toll-like receptor signaling pathways].

  2017cites this paper
• How to rewire the host cell: A home improvement guide for intracellular bacteria

  2017cites this paper
• How to rewire the host cell: A home improvement guide for intracellular bacteria.

  2017cites this paper
• How to rewire the host cell: A home improvement guide for intracellular bacteria

  2017cites this paper
• How to rewire the host cell: A home improvement guide for intracellular bacteria

  2017cites this paper
• How Do the Virulence Factors of Shigella Work Together to Cause Disease?

  2017cites this paper
• Shigella IpaH Family Effectors as a Versatile Model for Studying Pathogenic Bacteria

  2016cites this paper
• Shigella flexneri suppresses NF-kB activation by inhibiting linear ubiquitin chain ligation

  2016cites this paper
• E2 enzymes: more than just middle men

  2016cites this paper
• Modification of Bacterial Effector Proteins Inside Eukaryotic Host Cells

  2016cites this paper
• Implications of Spatiotemporal Regulation of Shigella flexneri Type Three Secretion Activity on Effector Functions: Think Globally, Act Locally

  2016cites this paper
• The bacterial pathogen–ubiquitin interface: lessons learned from Shigella

  2015cites this paper
• Subverting Toll-Like Receptor Signaling by Bacterial Pathogens

  2015cites this paper
• Cross Kingdom Activators of Five Classes of Bacterial Effectors

  2015cites this paper
• Bacterial Internalization, Localization, and Effectors Shape the Epithelial Immune Response during Shigella flexneri Infection

  2015cites this paper
• Shigella Manipulates Host Immune Responses by Delivering Effector Proteins with Specific Roles

  2015cites this paper
• Hijacking of death receptor signaling by bacterial pathogen effectors

  2015cites this paper
• Role of virulence factors on host inflammatory response induced by diarrheagenic Escherichia coli pathotypes.

  2015cites this paper
• Diversity of bacterial manipulation of the host ubiquitin pathways

  2015cites this paper
• Modulation of the host innate immune and inflammatory response by translocated bacterial proteins

  2015cites this paper
• Mechanisms by which Shigella flexneri impairs dendritic cell function: silencing the link between innate and adaptive immunity

  2015cites this paper
• Epithelial Immune Response during Shigella Infection

  2015cites this paper
• Development of a Proteomics Platform for Analysis of the Plant-pathogen Interface

  2015cites this paper
• Structural insight into effector proteins of Gram‐negative bacterial pathogens that modulate the phosphoproteome of their host

  2015influential citation
• Type III effector NleH2 from Escherichia coli O157:H7 str. Sakai features an atypical protein kinase domain.

  2014cites this paper
• Thinking outside the Osp(G)—kinase activation by E2‐ubiquitin

  2014influential citation
• Inhibition of death receptor signaling by bacterial gut pathogens.

  2014cites this paper
• Bacteria fighting back: how pathogens target and subvert the host innate immune system.

  2014cites this paper
• Have you seen ? Thinking outside the Osp ( G ) — kinase activation by E 2-ubiquitin

  2014influential citation
• Bacterial Serine/Threonine Protein Kinases in Host-Pathogen Interactions*

  2014cites this paper
• Structural basis for the inhibition of host protein ubiquitination by Shigella effector kinase OspG.

  2014influential citation
• E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis

  2014cites this paper
• Vibrio Type III Effector VPA1380 Is Related to the Cysteine Protease Domain of Large Bacterial Toxins

  2014cites this paper
• Exploitation of the host ubiquitin system by human bacterial pathogens

  2014cites this paper
• Subversion of trafficking, apoptosis, and innate immunity by type III secretion system effectors.

  2013cites this paper
• What pathogens have taught us about posttranslational modifications.

  2013influential citation