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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

  • Sulfonated rhodamines as impermeable labelling substrates for cell surface protein visualization

    • Authors : Birke, Ramona (2021)

  • Sulfonated rhodamines that endow xanthene dyes with cellular impermeability are presented. We fuse charged sulfonates to red and far-red dyes to obtain Sulfo549 and Sulfo646, respectively, and further link these to SNAP- and Halo-tag substrates for protein self-labelling. Cellular impermeability is validated in live cell imaging experiments in transfected HEK cells and neurons derived from induced pluripotent stem cells (iPSCs). Lastly, we show that&...
  • Journal article

  • TDFragMapper: a visualization tool for evaluating experimental parameters in top-down proteomics

    • Authors : Dhenin, Jonathan (2021)

  • Top-down proteomics (TDP) is a powerful technology allowing the char acterization of proteins at the proteoform level using high-resolution tan dem mass spectrometry (MS/MS). Proteoforms correspond to the different forms of a protein arising from all combinatorial sources of variation from a single gene (including combinations of genetic variation, alternative splicing, and post-translational modifications)(Smith and Kelleher, 2018). The complete...
  • 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...
  • Journal article

  • Binding mechanism underlying FIH-1 suppression caused by the N-terminal disordered region of Mint3

    • Authors : Ten, Tensho (2021)

  • Mint3 is known to enhance aerobic ATP production, known as the Warburg effect, by binding to FIH-1. Since this effect is considered to be beneficial for cancer cells, the interaction is a promising target for cancer therapy. However, previous research has suggested that the interacting region of Mint3 with FIH-1 is intrinsically disordered, which makes investigation of this interaction challenging. Therefore, we adopted a physicochemical approach that co...