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Cyanopyridylalanines are non-canonical amino acids that react with aminothiol compounds under physiological conditions in a biocompatible manner without requiring added catalyst. Here we present newly developed aminoacyl-tRNA synthetases for genetic encoding of meta- and para-cyanopyridylalanine to enable the site-specific attachment of a wide range of different functionalities. The outstanding utility of the cyanopyridine moiety is demonstrated by examples of i) post-translational functionalization of proteins, ii) in-cell macrocyclization of peptides and proteins, and iii) protein stapling. The biocompatible nature of the protein ligation chemistry enabled by the cyanopyridylalanine amino acid opens a new path to specific in vivo protein modifications in complex biological environments.
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http://dx.doi.org/10.1002/anie.202114154 | DOI Listing |
Sci Adv
September 2025
Frontiers Science Center for Molecular Design Breeding, Key Laboratory of Crop Heterosis and Utilization (MOE), Beijing Key Laboratory of Crop Genetic Improvement, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China.
Grain size substantially influences rice quality and yield. In this study, we identified (), a quantitative trait locus encoding an F-box protein that enhances grain length by promoting cell proliferation. The transcription factor OsbZIP35 represses expression, while COR1 interacts with OsTCP19, leading to its degradation.
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September 2025
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
(phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including , , , and , even in the absence of IFN-γ stimulation in vitro.
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September 2025
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA.
Understanding how cells control their biophysical properties during development remains a fundamental challenge. While macromolecular crowding affects multiple cellular processes in single cells, its regulation in living animals remains poorly understood. Using genetically encoded multimeric nanoparticles for in vivo rheology, we found that tissues maintain mesoscale properties that differ from those observed across diverse systems, including bacteria, yeast species, and cultured mammalian cells.
View Article and Find Full Text PDFSci Transl Med
September 2025
Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Human B cell immunity to the influenza hemagglutinin (HA) stem, a universal vaccine target, is often stereotyped and immunogenetically restricted, posing hurdles to study outside of humans. Here, we show that cynomolgus macaques vaccinated with an HA stem immunogen elicit humanlike public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from V1-138, the macaque homolog of human V1-69, a V gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs).
View Article and Find Full Text PDFPLoS One
September 2025
Laboratório de Termitologia, Departamento de Sistemática e Ecologia, Centro de Ciências Exatas e da Natureza, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.
With the aim of expanding the possibilities of identifying termite species, in the present study we generated genetic data based on sequences of the mitochondrial gene encoding cytochrome c oxidase subunit II (COII) for termites (Blattodea: Isoptera) occurring in the state of Paraíba, northeastern Brazil. The genetic data were obtained from 135 COII sequences identified in 28 genera and 48 species. These are the first COII sequences for 15 taxa (31.
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