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  • Journal Article

  • Urine-HILIC: Automated sample preparation for bottom-up urinary proteome profiling in clinical proteomics

    • Authors : Govender, Ireshyn (2023)

  • The study of the human urinary proteome is becoming increasingly popular in clinical proteomics studies. Large volumes of samples are readily available with minimal invasiveness, and, in addition, soluble proteins and peptides de- rived from various tissues and organs are also filtered in urine, which can reflect more general health problems [1]. Plasma was long considered the best biofluid choice for biomarker discovery studies. However, the main ...
  • 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

  • A global, integrated view of the ubiquitylation site occupancy and dynamics

    • Authors : Prus, Gabriela (2023)

  • Ubiquitylation regulates virtually all proteins and biological processes in a cell. However, the global site-specific occupancy (stoichiometry) and turnover rate of ubiquitylation have never been quantified. Here, we present the first integrated picture of ubiquitylation site occupancy and half-life. Ubiquitylation occupancy spans four orders of magnitude, but the median ubiquitylation site occupancy is three orders of magnitude lower than that of 20...
  • Journal Article

  • Ubiquitin-derived artificial binding proteins targeting oncofetal fibronectin reveal scaffold plasticity by β-strand slippage

    • Authors :  Katzschmann, Anja (2023)

  • Affilin proteins (artificial binding proteins based on the ubiquitin scaffold) were generated using directed protein evolution to yield de‐novo variants that bind the extra‐domain B (EDB) of oncofetal fibronectin, an abundant tumor marker in fetal and neoplastic tissues. Structures of two EDB‐specific Affilin molecules reveal striking structural plasticity of the ubiquitin scaffold, characterized by β‐strand slippage, leading to diverse register shifts of ...
  • Journal Article

  • Identifying Selectivity Filters in Protein Biosensor for Ligand Screening

    • Authors : Sahil, Mohammad (2023)

  • Bacterial transcription initiation mainly occurs via two diverse RNA polymerases, namely 70 and 54. While 70 polymerase transcribes housekeeping genes and does not require any external activation to form transcriptionally competent open complex, the alternate polymerase 54 require regulatory proteins, typically AAA+ ATPases, that aid in converting the closed RNA polymerase complex to an active open state.1,2 External stimuli and enviro...
  • 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

  • DTX3L and USP28 fine-tune DNA double strand repair through mutual regulation of their protein levels

    • Authors : Ashok, Yashwanth (2023)

  • The DNA damage response involves a complex protein network with members mediating different post-translational modifications such as ubiquitination and deubiquitination. Thereby the E3 ubiquitin ligase DTX3L as well as the deubiquitinase USP28 are recruited especially to DNA double strand breaks (DSBs) suggesting mutual functional interactions. Here we present evidence for the existence of such crosstalk. Mechanistically we show that DTX3L interacts with USP28 and ubiq...
  • Journal Article

  • Exploring the Theoretical Propensity for Liquid-Liquid Phase Separation in the Organization of Golgi Matrix Proteins

    • Authors : Mendes, Luis Felipe S.; Costa-Filho, Antonio J. (2023)

  • Eukaryotic cells evolved to possess efficient secretory machinery capable of transporting a significant fraction of their proteome. The number of proteins predicted to enter the secretory pathway can reach up to 36% of the total proteome in humans (1). Proteins entering the secretory pathway are efficiently sorted to a specific destination: the extracellular space, the plasma membrane, or the interior of the endomembrane system. The machinery also has&#x...
  • Journal Article

  • Borrelia PeptideAtlas: A proteome resource of common Borrelia burgdorferi isolates for Lyme research

    • Authors : Reddy, Panga Jaipal. (2023)

  • Lyme disease , caused by an infection with the spirochete Borrelia burgdorferi, is the most common 36 vector-borne disease in North America. B. burgdorferi strains harbor extensive genomic and 37 proteomic variability and further comparison is key to understanding the spirochetes infectivity and 38 biological impacts of identified sequence variants. To achieve this goal, both transcript and mass 39 spectrometry (MS)-based proteomics was applied to assemble pe...