CelR is a transcriptional regulator that controls the expression of cellulases catalyzing cellulose hydrolysis. However, the structural mechanism of its regulation has remained unclear. Here, we report the first structure of CelR, in this case with cellobiose bound. CelR consists of a DNA-binding domain (DBD) and a regulatory domain (RD), and homodimerizes with each monomer bound to cellobiose. A hinge region (HR) in CelR connects the DBD with the RD, and Leu59 in the HR acts as a 'leucine lever' that transduces a transcriptional activation signal. Furthermore, an α4 helix mediates the ligand-binding signal for transcriptional activation. Tyr84 and Gln301 can potentially alter the ligand specificity of CelR. This study provides a pivotal step toward understanding transcription of the cellulases.
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http://dx.doi.org/10.1002/1873-3468.13206 | DOI Listing |
Neurotox Res
January 2025
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Resveratrol, a natural polyphenol, has shown promising neuroprotective effects in several in vivo and in vitro experimental models. However, the mechanisms by which resveratrol mediates these effects are not fully understood. Glutamate is the major excitatory neurotransmitter in the brain; however, excessive extracellular glutamate levels can affect neural activity in several neurological diseases.
View Article and Find Full Text PDFAntioxid Redox Signal
January 2025
Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
Hypoxia ischemia (HI) is a leading cause of cerebral palsy and long-term neurological sequelae in infants. Given that mitochondrial dysfunction in neurons contributes to HI brain damage, this study aimed to investigate the regulatory role of miR-9-5p in mitochondrial function following HI injury. Overexpression of miR-9-5p in HI mice or HO-exposed PC12 cells suppressed neuronal injury, associated with increased mitochondrial copy number, normalizing mitochondrial membrane potential, improved nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activation, and downregulation of Keap1.
View Article and Find Full Text PDFImmun Inflamm Dis
January 2025
Department of Medical Biochemistry, Institute of Health, Dambi Dollo University, Dambi Dolo, Ethiopia.
Background: The pathomechanism of blast traumatic brain injury (TBI) and blunt TBI is different. In blast injury, evidence indicates that a single blast exposure can often manifest long-term neurological impairments. However, its pathomechanism is still elusive, and treatments have been symptomatic.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
MOE Key Laboratory of Evolution & Marine Biodiversity and Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China.
DNA N6-methyladenine (6mA) is a potential epigenetic mark involved in gene transcription in eukaryotes, yet the regulatory mechanism governing its methyltransferase (MTase) activity remains obscure. Here, we exploited the 6mA MTase AMT1 to elucidate its auto-regulation in the unicellular eukaryote Tetrahymena thermophila. The detailed endogenous localization of AMT1 in vegetative and sexual stages revealed a correlation between the 6mA reestablishment in the new MAC and the occurrence of zygotically expressed AMT1.
View Article and Find Full Text PDFUnlabelled: The Sarm1 NAD hydrolase drives neurodegeneration in many contexts, but how Sarm1 activity is regulated remains poorly defined. Using CRISPR/Cas9 screening, we found loss of VHL suppressed Sarm1-mediated cellular degeneration. VHL normally promotes O -dependent constitutive ubiquitination and degradation of hypoxia-inducible factor 1 (HIF-1), but during hypoxia, HIF-1 is stabilized and regulates gene expression.
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