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  • Journal article

  • Deubiquitinase-Targeting Chimeras for Targeted Protein Stabilization

    • Authors : Henning, Nathaniel J. (2021)

  • Targeted protein degradation is a powerful therapeutic modality that uses heterobifunctional small-molecules to induce proximity between E3 ubiquitin ligases and target proteins to ubiquitinate and degrade specific proteins of interest. However, many proteins are ubiquitinated and degraded to drive disease pathology; in these cases targeted protein stabilization (TPS), rather than degradation, of the actively degraded target using a smallmolecule would be ther...
  • Journal article

  • Influence of the TorD signal peptide chaperone on Tat-dependent protein translocation

    • Authors : Bageshwar, Umesh K. (2021)

  • The twin-arginine translocation (Tat) pathway transports folded proteins across energetic membranes. Numerous Tat substrates contain co-factors that are inserted before transport with the assistance of redox enzyme maturation proteins (REMPs), which bind to the signal peptide of precursor proteins. How signal peptides are transferred from a REMP to a binding site on the Tat receptor complex remains unknown. Since the signal peptide mediates both ...
  • Journal article

  • Structural probing of Hsp26 activation and client binding by quantitative cross-linking mass spectrometry

    • Authors : Fürsch, Julius (2021)

  • Small heat-shock proteins (sHSP) are important members of the cellular stress response in all species. Their best described function is the binding of early unfolding states and the resulting prevention of protein aggregation. Most sHSPs exist as oligomers but vary in size and subunit organization. Many sHSPs exist as a polydisperse composition of oligomers which undergoes changes in subunit composition, folding status and rel...
  • Journal article

  • Stability of ligand-induced protein conformation influences affinity in maltose-binding protein

    • Authors : Noort, Marco van den (2021)

  • Our understanding of what determines ligand affinity of proteins is poor, even with highresolution structures available. Both the non-covalent ligand-protein interactions and the relative free energies of available conformations contribute to the affinity of a protein for a ligand. Distant, non-binding site residues can influence the ligand affinity by altering the free energy difference between a ligand-free and ligand-bound conformation. Our hypothesis isthat...
  • 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

  • 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

  • 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...
  • Journal Article

  • Flexibility and distributive synthesis regulate RNA priming and handoff in human DNA polymerase α-primase

    • Authors : Cordoba, John J (2023)

  • In eukaryotes, DNA polymerase α-primase (pol-prim) initiates DNA synthesis during replication, generating the first ~30 nucleotides of nascent strands.1–5 Pol-prim is unique among replicative polymerases in its ability to perform de novo synthesis from a single-stranded DNA template; the primers it creates are required for further synthesis by the processive polymerases ε and δ that perform the bulk of nascent strand synthesis6,7. Pol-prim plays a particularly...
  • Journal Article

  • A widespread proteinaceous sulfur storage compartment in bacteria

    • Authors : Benisch, Robert (2023)

  • Intracellular compartmentalization is essential for all cells and enables the regulation and optimization of metabolism1. One of the main functions of subcellular compartments is the storage of nutrients2-4. As bacteria do generally not possess membrane-bound organelles, they often have to rely on functionally analogous protein-based compartments2,5-7. Encapsulin nanocompartments are one of the most prevalent protein-based compartmentalization strategies found in prokaryotes5,8. Here ...