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  • Industry article

  • Anti-CRISPR protein mediated degradation of Cas9 in human cells

    • Authors : Tacca, Luisa Arake de (2023)

  • Bacteriophages encode anti-CRISPR (Acr) proteins that inactivate CRISPR-Cas bacterial8 immune systems, allowing successful invasion, replication, and prophage integration. Acr9 proteins inhibit CRISPR-Cas systems using a wide variety of mechanisms. AcrIIA1 is encoded by10 numerous phages and plasmids, binds specifically to the Cas9 HNH domain, and was the first11 Acr discovered to inhibit SpyCas9. Here we report the observation of AcrIIA1-induced degradation12 ...
  • Journal Article

  • USP16 is an ISG15 cross-reactive deubiquitinase targeting a subset of metabolic pathway-related proteins

    • Authors : Gan, Jin (2023)

  • The ubiquitin-like modifier ISG15 can modulate host and viral proteins to restrict viral and microbial infections, and act as a cytokine. Its expression and conjugation are strongly upregulated by type I interferons. Here we identify the deubiquitinating enzyme USP16 as an ISG15 cross-reactive protease. Ubiquitin-specific protease 16 (USP16) was found to react with an ISG15 activity-based probe in pull-down experiments using chronic myeloid leu...
  • Journal Article

  • SARS-CoV-2 Nonstructural Proteins 3 and 4 tune the Unfolded Protein Response

    • Authors : Davies, Jonathan P. (2023)

  • Coronaviruses (CoV), including SARS-CoV-2, modulate host proteostasis through activation of stress-responsive signaling pathways such as the Unfolded Protein Response (UPR), which remedies misfolded protein accumulation by attenuating translation and increasing protein folding capacity. While CoV nonstructural proteins (nsps) are essential for infection, little is known about the role of nsps in modulating the UPR. We characterized the impact of SARS-CoV-2 ns...
  • Journal Article

  • Vibrio cholerae’s ToxRS Bile Sensing System

    • Authors : Gubensäk, N.  (2023)

  • Cholera represents a diarrheal disease caused by the Gram-negative bacterium Vibrio cholerae. Its environmental persistence causing recurring sudden outbreaks is enabled by V. cholerae’s rapid adaption to changing environments involving sensory proteins like ToxR and ToxS. Located at the inner membrane, ToxR and ToxS react to environmental stimuli like bile acid, thereby inducing survival strategies e.g. bile resistance and virulence regulation. Currently, transcript...
  • Journal Article

  • Evolving spike-protein N-glycosylation in SARS-CoV-2 variants

    • Authors :  Baboo, Sabyasachi (2023)

  • UBR4 is an E3 ligase (E3) of the N-degron pathway and is involved in neurodevelopment, age-associated muscular atrophy and cancer progression. The location and mechanistic classification of the E3 module within the 600 kDa protein UBR4 remains unknown. Herein, we identify and characterize, at a biochemical and structural level, a distinct E3 module within human UBR4 consisting of a novel “hemiRING” zinc finger, a helical-rich UBR ...
  • Journal Article

  • Identification of the bacteriophage nucleus protein interaction network

    • Authors : Enustun, Eray (2023)

  • In the arms race between bacteria and bacteriophages (phages), some large-genome jumbo phages have evolved a protein shell that encloses their replicating genome to protect it against DNA-targeting immune factors. By segregating the genome from the host cytoplasm, however, the “phage nucleus” introduces the need to specifically transport mRNA and proteins through the nuclear shell, and to dock capsids on the shell for genome packaging. �...
  • Periodicals (Báo – Tạp chí)

  • A survey of pairwise epistasis supports an outside-in hierarchy of clade-specifying and function-defining residues in PSD95 PDZ3

    • Authors : Nedrud, David; Maestas, Willow Coyote; Schmidt, Daniel (2020)

  • Deep mutational scanning enables data-driven models of protein structure and function. Here, we adapted Saturated Programmable Insertion Engineering as an economical and programmable deep mutational scanning technique. We validate this approach with an existing single mutant dataset in the PSD95 PDZ3 domain, and further characterize most pairwise double mutants to study how a mutation’s phenotype depends on mutations at other sites, a phenomenon called epistasis. ...