Trends in Biochemical Sciences最新文献

Plants growing in fluctuating environments require dynamic coordination between carbon availability and growth-stress decisions. Trehalose-6-phosphate (Tre6P), a sugar signal linked to sucrose status, helps coordinate these decisions by regulating SUCROSE NON-FERMENTING 1-RELATED KINASE 1 (SnRK1)- and TARGET OF RAPAMYCIN (TOR)-dependent growth programs. Here, we synthesize recent advances in photosynthetic carbon dynamics, carbon sensing, and Tre6P-SnRK1-TOR signaling, highlighting emerging regulatory layers including Class II TREHALOSE PHOSPHATE SYNTHASE proteins, SnRK1 compartmentalization, and stress-associated TOR regulation. We further discuss how different photosynthetic strategies of carbon fixation, including C3, C4, and crassulacean acid metabolism, as well as UV-B signaling through UV RESISTANCE LOCUS 8, influence carbon-energy signaling. Finally, we outline unresolved questions relevant to crop resilience under fluctuating environments.

Modern-day group leaders are expected to excel not only in scientific research and teaching but also in leadership and in providing a safe and intellectually stimulating environment for the next generation of budding scientists. In this article, we explore the evolution of a modern-day group leader within and beyond the scientific community.

Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase expressed in pre-B and pre-T cells that functions in V(D)J recombination to add random nucleotides in a template-independent (TI) mode at junctions between antigen receptor gene segments. However, cellular, biochemical, and structural studies have also revealed a significant, short-length, template-dependent (TD) mode of TdT, in which it takes instructions from a template strand across a double-strand break. Here, we propose that this can occur through an intrachain fold-back synthesis to generate the short inverted repeats at V(D)J recombination junctions observed in early human lymphoid cells and within the adult human antigen receptor repertoire. This duality is also relevant to the functional and structural flexibility observed during the DNA repair process known as nonhomologous DNA end joining (NHEJ).

Carbon dioxide (CO₂) is a bioactive gas essential for several physiologically important biological processes, including metabolism, acid-base homoeostasis, and chemosensing. CO₂ can directly modulate these processes by stimulating or inhibiting specific cell signalling pathways, including the nuclear factor-κB, calcium, and Wingless (Wnt) pathways. One mechanism by which CO₂ interacts with proteins to modulate cell signalling is through the reversible and nonenzymatic modification of α- N-terminal and lysine ε-amino groups to form the carbamate post-translational modification (PTM). Identifying carbamate PTMs is technically challenging because these modifications are readily reversible. However, emerging techniques have now made possible their identification and functional characterisation. Here, we review recent advances in experimental and computational methods to identify CO₂-mediated PTMs.

A weakness in glycobiology research is the insufficient integration of approaches used to connect glycan structure to function. From glycogene knockouts to understanding glycan structures, dynamics, and interactions, to determining whether a single glycan structure underlies a specific cellular function, no single approach provides sufficient information to establish these relationships. We argue that resolving glycan structure-function relationships requires the integration of complementary approaches spanning genetics, analytical glycomics, glycoengineering, structural biology, and computational modelling. The field stands at a transition point: from cataloguing glycan structures to understanding their diverse roles in regulating the biology of health and disease. Such an integrated approach will be critical for translating structural glycan information into mechanistic insights and, ultimately, informed glycoengineering and therapeutic design.

Predictions of cysteine reactivity rely heavily on acidity (pK_a) data from dilute solutions. However, the intracellular milieu is crowded and dynamic, with substrates, cofactors, and metabolites that modulate reactivity, thereby affecting cell signaling and metabolic adaptation. This forum argues that Cys pK_a values are necessary but insufficient, proposing an integrated, microenvironment-dependent framework.

Protein phosphorylation is a central and reversible mechanism regulating virtually all cellular processes and is classically mediated by the canonical protein kinome and phosphatome. However, beyond their traditional roles as metabolic catalysts, a subset of metabolic enzymes also exhibits noncanonical 'moonlighting' activities as protein kinases or phosphatases, directly linking metabolic states to phosphorylation-dependent signaling. These unexpected functions of enzymes involved in glucose, fructose, lipid, nucleotide, and creatine metabolism influence a broad spectrum of cellular processes, including chromatin remodeling, transcription, cell cycle progression, metabolism, autophagy, cell survival and death, and immune responses. As a result, metabolic enzymes are increasingly recognized as key regulators that bridge cellular metabolism and signaling networks, with important implications for both normal physiology and disease.

Roots navigate soils where abiotic cues intersect with microbial activity. How they extract directional information from microbial processes remains unclear. Bao et al. identify saprotropism, whereby decay-generated pH gradients steer roots via the root meristem growth factor (RGF)-RGF receptor-abscisic acid signaling, revealing how ecological complexity shapes developmental decisions.

Intramembrane proteases catalyze peptide bond hydrolysis within cellular membranes, regulating processes including signaling, protein quality control, and membrane protein turnover. Recent advances in cryo-electron microscopy, biochemistry, and molecular dynamics simulations have transformed our understanding of how these enzymes recognize and process substrates within the lipid bilayer. Here, we discuss how dynamic interactions among proteases, substrates, and membranes govern substrate recognition. Structural and biophysical studies reveal how conformational dynamics, membrane remodeling, and specific protease-substrate interactions enable processing of membrane-embedded substrates. Studies of rhomboid pseudoproteases further suggest that transmembrane-domain recognition represents a conserved principle of membrane protein processing that extends beyond proteolysis itself. Finally, we consider how recognition determines membrane protein fate, linking protease activity to signaling, proteostasis, and nonproteolytic scaffolding functions.