Orientia tsutsugamushi Ank5 directs ubiquitination and proteasomal degradation of NLRC5 to inhibit major histocompatibility complex class I expression
Adcox, H.; Hunt, J. R.; Rodino, K. G.; Ottens, A. K.; Carlyon, J. A.
Show abstract
How intracellular bacteria subvert the major histocompatibility complex (MHC) class I pathway is poorly understood. Here, we show that the obligate intracellular bacterium Orientia tsutsugamushi uses its effector protein, Ank5, to orchestrate proteasomal degradation of the MHC class I gene transactivator, NLRC5. Ank5 uses a tyrosine in its fourth ankyrin repeat to bind the NLRC5 N-terminus while its F-box directs host SCF complex ubiquitination of K1194 in the leucine-rich repeat region that dictates NLRC5 susceptibility to Orientia- and Ank5-mediated degradation. The ability of O. tsutsugamushi strains to degrade NLRC5 correlates with ank5 genomic carriage. Ectopically expressed Ank5 that can bind but not degrade NLRC5 protects the transactivator during Orientia infection. Thus, Ank5 is an immunoevasin that uses its bipartite architecture to rid host cells of NLRC5 and MHC class I molecules. This study offers insight into how intracellular pathogens can impair MHC class I expression to benefit their survival.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The type 3 secretion system requires actin polymerization to open translocon pores 95%
- Toxoplasma gondii subverts the host ESCRT machinery for parasite uptake of host cytosolic proteins 95%
- Inducible CRISPR activation screen for interferon-stimulated genes identifies OAS1 as a SARS-CoV-2 restriction factor 95%
Similar papers in this journal
- Interferon-Inducible Guanylate-Binding Protein 5 Inhibits Replication of Multiple Viruses by Binding to the Oligosaccharyltransferase Complex and Inhibiting Glycoprotein Maturation 95%
- Interferon-responsive genes are targeted during the establishment of human cytomegalovirus latency 95%
- DAZAP2 functions as a pan-coronavirus restriction factor by inhibiting viral entry and genomic replication 95%
Similar papers in this journal
- Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen 96%
- Proximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by the E3 ubiquitin ligase PJA2 96%
- A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models 96%
Similar papers in this journal
- Trehalose dimycolate inhibits phagosome maturation and promotes intracellular M. tuberculosis growth via noncanonical SNARE interaction 95%
- Crystal structure of a guanine nucleotide exchange factor encoded by the scrub typhus pathogen Orientia tsutsugamushi 95%
- CRISPR with Transcriptional Readout reveals influenza transcriptionis modulated by NELF and can precipitate an interferon response 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.