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  • 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

  • Thiaproline accelerates the slow folding phase of proteins containing cis prolines in the native state by two orders of magnitude

    • Authors : Loughlin, Jennie O’ (2023)

  • The cis/trans isomerization of peptidyl-prolyl peptide bonds is often the bottleneck of the refolding reaction for proteins containing cis proline residues in the native state. Proline (Pro) analogues, especially C4-substituted fluoroprolines, have been widely used in protein engineering to enhance the thermodynamic stability of peptides and proteins and to investigate folding kinetics. 4-thiaproline (Thp) has been shown to bias the ring pucker of Pro, to inc...
  • 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 Spike Protein Fragment eases Amyloidogenesis of α-Synuclein

    • Authors : Chesney, Andrew D (2023)

  • Parkinson’s Disease is accompanied by presence of amyloids in the brain formed of α-synuclein chains. Correlation between COVID-19 and the onset of Parkinson’s disease let to the idea that amyloidogenic segments in SARS-COV-2 proteins can induce aggregation of α-synuclein. Using molecular dynamic simulations, we show that the fragment FKNIDGYFKI of the spike protein, which is unique for SARS-COV-2, shifts preferentially the ensemble of α-synuclein&#x...
  • 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...