Trends in Biochemical Sciences最新文献

Proteins drive most cellular functions and are key players in diseases, yet proteomics still lags behind genomics due to the complexity, diversity, and dynamic nature of proteoforms. Nanopore technology - known for real-time, single-molecule DNA sequencing - is a promising contender to revolutionize protein analysis. The method has recently been adapted to proteins, showing strong potential for protein identification. However, true de novo protein sequencing with nanopores remains an open challenge. This review compares current nanopore-based strategies for protein analysis and highlights their technical hurdles towards application. Additionally, engineering strategies are explored aiming to bridge the gap towards single-molecule protein analysis and sequencing.

A flurry of recent structural studies have focused on the polymerase complex of the deadly zoonotic pathogen Nipah virus (NiV). These include a report by Sala et al. describing an RNA duplex-bound state. This structure constitutes a snapshot of the complex in an early elongation step of the RNA synthesis cycle.

Plastics, especially polyethylene terephthalate (PET), are vital in modern life, with global production exceeding 400 million tons annually. This extensive use has led to significant plastic waste pollution, highlighting the need for effective recycling strategies. PET, one of the most recycled plastics, is a prime candidate for degradation into its original monomers through engineered PET hydrolases - enzymes with industrial potential. While previous engineering efforts have mainly focused on enhancing thermostability and catalytic efficiency, the crucial aspect of enzyme adsorption to PET surfaces has received less attention. This review specifically addresses the mechanisms of enzyme adsorption, detailing relevant experimental methods and simulation techniques while emphasizing the potential for engineering more effective PET hydrolases.

A recent report by Harlington et al. introduces SyoA, a cytochrome P450 enzyme that efficiently removes a methyl group from the S-subunits of lignin. Lignin is one of the most abundant forms of renewable carbon on Earth. Methyl removal is essential to strategies for biologically converting lignin into useful chemicals.

Cellular dormancy is characterized by a prolonged, reversible cell cycle arrest and absence of growth. Dormancy allows organisms to endure unfavorable environmental conditions and to maintain long-lived quiescent progenitor cells essential for tissue homeostasis and reproduction. Protein homeostasis (proteostasis) is central to the maintenance of intracellular integrity in all cell types, particularly in long-lived, non-dividing cells. Here we review adaptations to support proteostasis in dormant cells and highlight common themes of cellular dormancy across organisms, from yeast to adult quiescent stem cells. We also feature vertebrate oocytes as an emerging model of proteostasis during dormancy. Together, these comparisons reveal common and unique strategies to sustain proteostasis during dormancy, offering insights into how cells preserve function and viability over long quiescence periods.

Histones are fundamental chromatin-organizing proteins in eukaryotes and archaea, where they assemble into (hyper)nucleosomes that wrap DNA. Recent studies have expanded the known repertoire of histones, identifying new variants in both prokaryotes and large DNA viruses. In prokaryotes, histones exhibit a range of DNA-binding modes, including wrapping, bending, and bridging, rather than exclusively forming nucleosomes. Notably, large DNA viruses encode histone paralogs that structurally resemble eukaryotic core histones and assemble into nucleosome-like complexes. This review summarizes recent discoveries on canonical archaeal nucleosomal histones and newly identified histones in archaea, bacteria, and viruses, highlighting their structural and functional diversity in genome organization.

The hypoxia-inducible factors (HIFs) are central transcriptional mediators of the cellular response to hypoxia. HIF activation typically drives a physiologically beneficial adaptive response to hypoxia. However, within solid tumors, the HIF-driven adaptation to hypoxia results in alterations within major cancer cell signaling axes, including those regulating angiogenesis, metabolism, and immune modulation, which profoundly impact tumor progression. This review describes established and recent findings of the role of HIFs in the regulation of these major axes, and the impact of the 'HIF axes' on tumor progression and response to therapy. Current and emerging therapies targeting these axes will also be discussed.

Ferroptosis is a distinctive form of regulated cell death driven by iron-dependent phospholipid peroxidation. Its initiation and suppression are finely tuned by metabolic pathways, transcription factors, and nuclear receptors that control lipid peroxidation levels. Significantly, nutrients such as vitamins and trace elements play a pivotal role in this regulation, directly linking diet and nutrients to cellular fate. This review conveys the latest insights into the metabolic components that influence ferroptosis. We highlight how metabolic and transcriptional regulators and key nutrients, micronutrients, and metabolites orchestrate this process. Charting these interactions will be essential for developing new avenues for therapeutic interventions targeting ferroptosis in various diseases.