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Showing results 1 to 10 of 10
  • OER000002285.pdf.jpg
  • Journal Article

  • A robust method for measuring aminoacylation through tRNA-Seq

    • Authors : Davidsen, Kristian (2023)

  • Current methods to quantify the fraction of aminoacylated tRNAs, also known as the 8 tRNA charge, are limited by issues with either low throughput, precision, and/or accuracy. Here, we 9 present an optimized charge tRNA-Seq method that combines previous developments with newly 10 described approaches to establish a protocol for precise and accurate tRNA charge measurements. 11 We verify that this protocol provides robust quantification ...
  • OER000002427.pdf.jpg
  • Ebooks (Sách điện tử)

  • A TREX1 model reveals double-strand DNA preference and inter-protomer regulation

    • Authors : Hemphill, Wayne O. (2023)

  • The TREX1 3’ à 5’ exonuclease degrades DNA in vivo to prevent chronic immune activation through the cGAS-STING pathway. TREX1 degrades ss- and dsDNA containing a free 3’-hydroxyl, but the precise nature of immune-activating DNA remains an open question. The TREX1 homodimer structure is critical for exonuclease activity with amino acids from one protomer acting across the dimer interface contributing to catalysis in the opposing protomer.&#x...
  • OER000002299.pdf.jpg
  • Journal Article

  • Application of monolayer graphene to cryo-electron microscopy grids for high-resolution structure determination

    • Authors : Grassetti, andrew V (2023)

  • The application of support layers, such as graphene, to cryo-electron microscopy grids can increase the density of particles imaged, limit particle interactions with the air-water interface, reduce the extent of beam-induced motion, and, in some instances, improve the distribution of particle orientations. This paper describes a robust protocol for coating cryo-EM grids with a monolayer of graphene for improved cryo-sample preparation. Single particle cryo...
  • OER000002296.pdf.jpg
  • Journal Article

  • Deep mutational scanning and machine learning uncover antimicrobial peptide features driving membrane selectivity

    • Authors : Randall, Justin R. (2023)

  • Host-defense peptides are an evolutionarily conserved group of natural antimicrobial peptides which fight pathogens through direct antimicrobial activity and/or by modulating the host immune response during infection1. Antibacterial host-defense peptides generally kill bacteria directly through cell membrane disruption, but many show difficulties differentiating bacterial and mammalian cell membranes, complicating clinical use. Though some aspects of membrane selectivity have been describ...
  • OER000002289.pdf.jpg
  • Journal Article

  • Probing Bioactive Chemical Space to Discover RNA-Targeted Small Molecules

    • Authors : wicks, sarah L. (2023)

  • The use of small molecules to modulate RNA structure and function has become invaluable for studying the many roles of RNA in biological processes1 as well as discovering effective therapeutic treatments.2-5 Early on, the promise of RNA as a ‘druggable’ target was demonstrated by the identification of several RNA-targeting small molecule classes such as aminoglycosides.6, 7 These ligands bound highly abundant and structured ribosomal RNA (r...
  • OER000002283.pdf.jpg
  • Journal Article

  • Protein Ensemble Generation through Variational Autoencoder Latent Space Sampling

    • Authors : Mansoor, Sanaa (2023)

  • Mapping the ensemble of protein conformations that contribute to function and can be targeted by small molecule drugs remains an outstanding challenge. Here we explore the use of soft-introspective variational autoencoders for reducing the challenge of dimensionality in the protein structure ensemble generation problem. We convert high-dimensional protein structural data into a continuous, low-dimensional representation, carry out search in this space guided&#...
  • OER000002307.pdf.jpg
  • Journal Article

  • Shared Structural Features of Miro Binding Control Mitochondrial Homeostasis

    • Authors : Covill-Cooke, Christian (2023)

  • Miro proteins are universally conserved mitochondrial calcium-binding GTPases that regulate a multitude of mitochondrial processes, including transport, clearance and lipid trafficking. Miro binds a variety of client proteins involved in these functions. How this binding is operated at the molecular level and whether and how it is important for mitochondrial health, however, remains unknown. Here, we show that known Miro clients all use a similar short motif&...
  • OER000002308.pdf.jpg
  • Journal Article

  • Surprising variety in the USP deubiquitinase catalytic mechanism

    • Authors : Keijzer, Niels (2023)

  • The USP family of deubiquitinases (DUBs) controls many ubiquitin-dependent signaling events. This generates therapeutic potential, with active-site inhibitors in preclinical and clinical studies. Understanding of the USP active site was so far primarily guided by USP7 data, where the catalytic triad consists of cysteine, histidine and a third residue (first critical residue), which polarizes the histidine through a hydrogen bond. A conserved aspartate (second critical&...
  • OER000002294.pdf.jpg
  • Journal Article

  • USING SMALL MOLECULES TO TURN AN RNA APTAMER INTO SENSORS FOR INORGANIC TARGETS WITHOUT IN VITRO SELECTION

    • Authors : aggarwal, Tushar (2023)

  • Aptamers are structured nucleic acid sequences that selectively bind a molecular target with high affinity. Aptamer sequences can be found in nature as gene regulation elements located in the untranslated regions of mRNAs,1 or discovered in the laboratory by in vitro selection (also known as SELEX: systematic evolution of ligands by exponential enrichment) from a random pool of nucleic acids.2,3 Some in vitroselected aptamers can bind ...