The AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis that initiates cytoplasmic maturation of the large ribosomal subunit. Drg1 releases the shuttling maturation factor Rlp24 from pre-60S particles shortly after nuclear export, a strict requirement for downstream maturation. The molecular mechanism of release remained elusive. Here, we report a series of cryo-EM structures that captured the extraction of Rlp24 from pre-60S particles by Saccharomyces cerevisiae Drg1. These structures reveal that Arx1 and the eukaryote-specific rRNA expansion segment ES27 form a joint docking platform that positions Drg1 for efficient extraction of Rlp24 from the pre-ribosome. The tips of the Drg1 N domains thereby guide the Rlp24 C terminus into the central pore of the Drg1 hexamer, enabling extraction by a hand-over-hand translocation mechanism. Our results uncover substrate recognition and processing by Drg1 step by step and provide a comprehensive mechanistic picture of the conserved modus operandi of AAA-ATPases.
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http://dx.doi.org/10.1038/s41594-022-00832-5 | DOI Listing |
Open Heart
January 2025
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
Background: The role of cyclic guanosine 3',5'-monophosphate (cGMP) after acute myocardial infarction (AMI) is not well understood despite its significance as a second messenger of natriuretic peptides (NPs) in cardiovascular disease. We investigated the association between the NP-cGMP cascade and left ventricular reverse remodelling (LVRR) in anterior AMI.
Methods: 67 patients with their first anterior AMI (median age, 64 years; male, 76%) underwent prospective evaluation of plasma concentrations of the molecular forms of A-type and B-type natriuretic peptide (BNP) and cGMP from immediately after primary percutaneous coronary intervention (PPCI) to 10 months post-AMI.
Biochem Biophys Res Commun
January 2025
Department of Pharmacology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan; Research Institute for Cell Design Medical Science, Yamaguchi University, Yamaguchi, Japan. Electronic address:
Impaired fracture healing in diabetic patients leads to prolonged morbidity and increased healthcare costs. Methylglyoxal (MG), a reactive metabolite elevated in diabetes, is implicated in various complications, but its direct impact on bone healing remains unclear. Here, using a non-diabetic murine tibial fracture model, we demonstrate that MG directly impairs fracture healing.
View Article and Find Full Text PDFAquat Toxicol
December 2024
Department of Chemistry and CICECO, Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. Electronic address:
In this study, untargeted Nuclear Magnetic Resonance (NMR) metabolomics was applied for the first time, to our knowledge, to assess the metabolic impact of direct and transgenerational exposure (F0 and F3 generations, respectively) of amphipods Gammarus locusta to simvastatin (SIM), a pharmaceutical widely prescribed for the treatment of hypercholesterolemia. Results revealed the important gender-dependent nature of each of these effects. Directly exposed males showed enhanced glucose catabolism and tricarboxylic acid (TCA) cycle activity, in tandem with adaptations in osmotic regulation and glyoxylate metabolism.
View Article and Find Full Text PDFNeuroimage
January 2025
State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100875, China. Electronic address:
Understanding the developmental trajectories of the auditory and visual systems is crucial to elucidate cognitive maturation and its associated relationships, which are essential for effectively navigating dynamic environments. Our one recent study has shown a positive correlation between the event-related potential (ERP) amplitudes associated with visual selective attention (posterior contralateral N2) and auditory change detection (mismatch negativity) in adults, suggesting an intimate relationship and potential shared mechanism between visual selective attention and auditory change detection. However, the evolution of these processes and their relationship over time remains unclear.
View Article and Find Full Text PDFXi Bao Yu Fen Zi Mian Yi Xue Za Zhi
January 2025
Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming 650500, China. *Corresponding authors, E-mail:
The innate immune response is the first line of defense for the host against viral infections. Targeted degradation of pathogenic microorganisms through autophagy, in conjunction with pattern recognition receptors synergistically inducing the production of interferon (IFN), constitutes an important pathway for the body to resist viral infections. Rubicon, a Run domain Beclin 1-interacting and cysteine-rich domain protein, has an inhibitory effect on autophagy and IFN production.
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