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http://dx.doi.org/10.1176/ps.47.7.697 | DOI Listing |
Nat Commun
January 2025
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Members of the piggyBac superfamily of DNA transposons are widely distributed in host genomes ranging from insects to mammals. The human genome has retained five piggyBac-derived genes as domesticated elements although they are no longer mobile. Here, we have investigated the transposition properties of piggyBat from Myotis lucifugus, the only known active mammalian DNA transposon, and show that its low activity in human cells is due to subterminal inhibitory DNA sequences.
View Article and Find Full Text PDFNat Commun
January 2025
Interdisciplinary Life Sciences Graduate Programs, University of Texas at Austin, Austin, TX, 78712, USA.
Type II CRISPR endonucleases are widely used programmable genome editing tools. Recently, CRISPR-Cas systems with highly compact nucleases have been discovered, including Cas9d (a type II-D nuclease). Here, we report the cryo-EM structures of a Cas9d nuclease (747 amino acids in length) in multiple functional states, revealing a stepwise process of DNA targeting involving a conformational switch in a REC2 domain insertion.
View Article and Find Full Text PDFArch Biochem Biophys
February 2025
Alberta RNA Research and Training Institute (ARRTI), University of Lethbridge, Lethbridge, AB, Canada; Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, AB, Canada. Electronic address:
A current challenge in the rational design of biomolecular sensors is the ability to custom design binding affinities and detection mode in silico. To this end, we re-engineered a previously reported computationally-designed fluorescent maltooligosaccharide (MOS)-detecting biosensor to both alter its ligand-binding affinity and to analyse the underlying sensing mechanism. The dynamic range of the biosensor was expanded through the computer aided introduction of a series of amino acid substitutions in the starting protein scaffold (MalX from Streptococcus pneumoniae), which generated a biosensor set with binding affinities spanning over five orders of magnitude.
View Article and Find Full Text PDFProtein Sci
December 2024
A.N. Bach Institute of Biochemistry, Federal Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia.
Recently, a number of message passing neural network (MPNN)-based methods have been introduced that, based on backbone atom coordinates, efficiently recover native amino acid sequences of proteins and predict modifications that result in better expressing, more soluble, and stable variants. However, usually, X-ray structures, or artificial structures generated by algorithms trained on X-ray structures, were employed to define target backbone conformations. Here, we show that commonly used algorithms ProteinMPNN and SolubleMPNN display low sequence recovery on structures determined using NMR.
View Article and Find Full Text PDFJ Clin Oncol
November 2024
NRG Oncology, Four Penn Center, Philadelphia, PA.
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