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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

  • CheSPI: Chemical shift Secondary structure Population Inference

    • Authors : Nielsen, Jakob Toudahl (2021)

  • NMR chemical shifts (CSs) are delicate reporters of local protein structure, and recent advances in random coil CS (RCCS) prediction and interpretation now offer the compelling prospect of inferring small populations of structure from small deviations from RCCSs. Here, we present CheSPI, a simple and efficient method that provides unbiased and sensitive aggregate measures of local structure and disorder. It is demonstrated that CheSPI can p...
  • Journal article

  • Comparative host interactomes of the SARS-CoV-2 nonstructural protein 3 and human coronavirus homologs

    • Authors : Almasy, Katherine M. (2021)

  • Human coronaviruses have become an increasing threat to global health; three highly pathogenic strains have emerged since the early 2000s, including most recently SARS-CoV-2, the cause of COVID-19. A better understanding of the molecular mechanisms of coronavirus pathogenesis is needed, including how these highly virulent strains differ from those that cause milder, common-cold like disease. While significant progress has been made in understanding how SARS-CoV-2 ...
  • Journal article

  • A biosensor to gauge protein homeostasis resilience differences in the nucleus compared to cytosol of mammalian cells

    • Authors : Raeburn, Candice B. (2021)

  • An extensive network of chaperones and other proteins maintain protein homeostasis and guard against inappropriate protein aggregation that is a hallmark of neurodegenerative diseases. Using a fluorescence resonance energy-based biosensor that simultaneously reports on intact cellular chaperone holdase activity and detrimental aggregation propensity, we investigated the buffering capacity of the systems managing protein homeostasis in the nucleus of the human cell l...
  • Journal article

  • HaloTag9: an engineered protein tag to improve fluorophore performance

    • Authors : Frei, Michelle S. (2021)

  • HaloTag9 is an engineered variant of HaloTag7 with up to 40% higher brightness and increased fluorescence lifetime when labeled with fluorogenic rhodamines. Moreover, combining HaloTag9 with HaloTag7 and other fluorescent probes enabled live-cell multiplexing using a single fluorophore and the generation of a fluorescence lifetime-based biosensor. The increased brightness of HaloTag9 and its use in fluorescence lifetime multiplexing makes it a...
  • Journal article

  • Development, validation, and application of the ribosome separation and reconstitution system for protein translation in vitro

    • Authors : Trainor, Brandon M. (2021)

  • The conventional view regarding regulation of gene expression is based on transcription control. However, a growing number of recent studies has revealed the important additional impact of translational regulation. Eukaryotic translational machinery appears to be capable of reprogramming mRNA translation to generate proteins required to maintain a healthy cellular proteostasis under particular physiological conditions or to adapt to stress. Altho...
  • Journal article

  • Tannic Acid Inhibits α-Synuclein Amyloid Fibril Formation via Binding to the Monomer N-terminal Domain

    • Authors : Stoeber, Jonathan (2021)

  • α-Synuclein (αS) is an intrinsically disordered protein (IDP) that aggregates into amyloid fibrils during the progression of Parkinson’s Disease and other synucleinopathies. The N-terminal domain (residues 1-60) is now understood to play a critical role in the initial nucleation of aggregation, as well as a pivotal role in the monomer-fibril interaction underlying amyloid seeding. Here we report on the interaction between αS and&#x...