Metabolites, beyond their canonical roles in energy production and biosynthesis, also serve as precursors for a diverse array of post-translational modifications (PTMs). The functional significance of PTMs in physiology and disease has attracted increasing attention, and the landscape of metabolite-mediated PTMs has expanded markedly in recent years. In this review, we summarize recently identified metabolite-mediated PTMs categorized by their diverse metabolic origins, along with their proteomic discoveries, regulations, and functions. We further highlight the utility of chemical proteomics in uncovering previously unrecognized PTMs and discuss current challenges in studying PTMs. Together, these advances enhance our understanding of the connection between metabolism and PTMs.
CRISPR-Cas systems in prokaryotes serve as adaptive immune systems that neutralize phage infections through RNA-guided nucleases. Immunization is achieved during the adaptation stage through Cas1-Cas2 integrase-mediated insertion of short foreign DNA snippets, termed spacers, into a CRISPR array in the host genome. This review examines the evolutionary origins of Cas1-Cas2 and the mechanisms of spacer acquisition in DNA-targeting CRISPR-Cas systems. Particular emphasis is placed on the recently characterized effector-assisted adaptation pathways, in which CRISPR effector proteins, such as Cascade and Cas9, typically involved in target interference, are repurposed for prespacer capture and integration into a CRISPR array.
The flow of electrons is essential for life. To sustain metabolic flux, organisms efficiently transfer electrons to terminal electron acceptors, which range from inorganic nutrients to intracellularly derived organic metabolites. While the rise of atmospheric oxygen favored the expansion of high-yield aerobic respiration, the diversity of anaerobic electron acceptors remains important for organismal and ecological health, particularly in response to fluctuations in nutrient availability. This review summarizes respiratory and fermentative electron acceptors across eukaryotes, focusing on the evolution of anaerobic pathways. We highlight how ancient metabolic strategies have been conserved and modified to support organisms’ adaptation to diverse environmental niches and to sustain biological resilience.
As sessile organisms, plants rely on environmental cues to make key developmental decisions. These decisions are rarely based on a single time point but instead emerge through the integration of past and present experiences, a process broadly referred to as molecular memory. Canonical epigenetic mechanisms operating at the chromatin and RNA levels are often viewed as major drivers of plant molecular memory, yet whether plants also exploit changes in protein state remains an open and compelling question. In this opinion piece, we speculate that prion-like proteins (PrLPs) may function as memory molecules in plants. Through switchlike changes in conformation or assembly state, PrLPs may convert environmental experiences into persistent molecular states to enable future developmental responses.
Despite seemingly low levels of molybdenum (Mo)/tungsten (W) in the Earth's ancient oceans, these metals play central roles in driving modern biogeochemical cycles. Klos et al. used phylogenomic approaches to reconstruct the Mo/W biochemical repertoire over approximately 3.4 billion years, showing that ancient organisms used these metals early in Earth's history.
Cation channel of sperm (CatSper) is the principal Ca2+ entry pathway governing sperm hyperactivated motility, a process essential for successful fertilization and male fertility in sexually reproducing animals. Recent structural studies of native mouse CatSper, together with in situ analyses in mouse and human sperm, have transformed our understanding of how its unique multisubunit architecture underpins channel assembly, gating, and higher-order organization along the sperm flagellum. These advances have also provided insights into the evolutionary diversification of CatSper and the spatial organization of Ca2+ signaling required for sperm function. In this review, we summarize recent progress in elucidating CatSper structure, mechanism, evolution, and physiological function, and discuss the implications for male infertility and the structure-guided development of nonhormonal male contraceptives.
Proton extrusion by plasma membrane autoinhibited H+ ATPases (AHAs) enables stomatal opening and plant cell expansion. Takase et al. demonstrated that heterocomplexes of C5 and C7 RAF-like kinases activate AHAs. The modular nature of C5-C7 RAF complexes allows cell-type-specific responses to stimuli, such as stomatal guard-cell CO2 levels.
Because eukaryotic chromosomes are composed of linear DNA molecules, specialized mechanisms are required to ensure their protection and replication. Telomeres, consisting of multiple repeats of a simple DNA sequence and associated proteins, cap these chromosome ends. Telomeric DNA replication requires telomerase, a reverse transcriptase with an intrinsic RNA subunit that provides a template for synthesizing the DNA repeats. New technologies, including cryogenic electron microscopy and long-read DNA sequencing, have provided insights into telomere biology that motivate this review. Furthermore, mutations that impair the machinery responsible for the replication and protection of telomeres lead to telomere biology disorders, and activation of telomerase is a driver of diverse cancers. In this review, we describe how basic science is now informing therapeutic approaches to these diseases.
The framework and practical tools presented in this article enable neurodivergent scientists, mentors, research teams, and institutions to better understand the cognitive and environmental factors that shape scientific work. By normalizing transparency, continuous learning, and iterative improvement, this framework and its practical tools foster inclusive research cultures that unlock scientific potential and accelerate discovery.
Since 1964, the Federation of European Biochemical Societies has supported the molecular life sciences through scientific exchange, training, international collaboration, and publishing. This study provides an overview of the organisation's evolution, activities, initiatives, and its contributions to supporting researchers and scientific communities across Europe and beyond.
Scientific innovation thrives on diverse problem-solving for modern interdisciplinary challenges. Neurodivergent scientists provide unique perspectives essential for high-impact discovery. We use the 'Neurodiversity Iceberg' to show how cognitive strengths drive innovative research and to offer a plan for mentors and institutions to tap into the potential of their entire scientific workforce.
The endoplasmic reticulum (ER) membrane is both the central site of cellular lipid synthesis and the platform on which ER-associated degradation (ERAD) selects membrane proteins for ubiquitination and proteasomal destruction. ERAD shapes ER lipid composition by degrading biosynthetic enzymes and regulators of lipid metabolism, while the lipid environment in turn modulates each step of the pathway. In this review, we apply biophysical concepts of membrane protein dynamics to explain how changes in membrane composition shift conformational equilibria and bias proteostatic fate. We distinguish three modes through which lipid information reaches ERAD: substrate-intrinsic sensing, adaptor-mediated coupling, and lipid sensitivity of the ubiquitination machinery itself. These perspectives reframe ERAD as a lipid-responsive pathway integrating membrane composition with selective protein turnover.
Targeted protein degradation has rapidly evolved from a chemical biology concept into a therapeutic modality, with the first proteolysis-targeting chimera (PROTAC) degrader now approved as a medicine. Linkers play a central role in governing ternary complex formation and conferring drug-like properties on bifunctional compounds. However, linker optimisation remains one of the least rationalised steps in degrader design. In this review, we introduce a linkerology framework that integrates a data-driven analysis of PROTAC linker chemotypes with historical context, representative case studies, emerging proximity-based modalities, and clinical-stage trends. We reveal persistent biases in the explored linker space and identify linker features that are preferentially retained in clinical-stage degraders. Together, these insights position linkerology as a central discipline in PROTAC design and provide guidance for the development of next-generation proximity-based therapeutics.
The atmosphere is increasingly recognised as a major energy source supporting life. Numerous microbes, termed aerotrophs, use high-affinity enzymes to harvest energy from atmospheric hydrogen, carbon monoxide, and methane. This metabolism shapes atmospheric chemistry and sustains biodiversity across diverse ecosystems. This primer summarises the basis, roles, and significance of aerotrophy.
Forty years after the term 'RNA world' was coined, the RNA world hypothesis is best framed as an RNA-centered evolutionary phase rather than as an RNA-only biosphere. Recent advances in systems chemistry now turn several long-standing objections into experimentally measurable constraints. These include linking nucleotide activation with template copying, quantifying how wet-dry cycling and freeze-thaw cycles alter polymer growth, and testing how compartments change retention, exchange, and parasite control. In parallel, polymerase ribozymes now connect structure, processivity, fidelity, and sustained RNA-catalyzed evolution. Peptide ligation in water, thioester-mediated aminoacyl-RNA chemistry, peptidyl-RNA synthesis, and peptide effects on RNA folding support ribonucleoprotein models in which peptides are integrated partners in a coevolutionary process. Remaining bottlenecks define testable benchmarks in chemically heterogeneous RNA-centered systems.
Nipah virus (NiV) is a highly pathogenic, nonsegmented, negative-sense RNA virus (nsNSV) from the Mononegavirales order that causes frequent outbreaks, with no approved treatment available. Replication and transcription of its genome are carried out by a viral RNA-dependent RNA polymerase (RdRp) complex composed of the large catalytic protein (L) and the tetrameric phosphoprotein (P). Recently, structural insights into the NiV RdRp complex have emerged at an unprecedented pace. In particular, snapshots of the complex in precatalytic, early-elongation, and inhibitor-bound states have been reported. In this article, we review how these data shed light on the molecular mechanisms of RNA synthesis and inhibition in NiV and explore how these insights expand our understanding of nsNSV RdRps in general.
