Reviews & Analysis

Understanding how metals contribute to brain function is a major health priority. A new study combining pharmacology and genetics implicates the accumulation of copper in a brain arousal center as a regulator of zebrafish activity.

Single-molecule techniques combined with molecular dynamics simulations allowed visualization of a surprisingly high level of conformational homogeneity in the transport cycle of an ABC import system, BtuCD-F, and revealed an unexpected tight coupling of distinct conformational states responsible for vitamin B₁₂ binding, transport and release.

This Perspective explores the diversity, mechanisms and practical aspects of natural and engineered CRISPR-associated nucleases for genome engineering applications.

The ability to subvert E3 ubiquitin ligases with small-molecule drugs offers tremendous promise for drug discovery. A new study demonstrates how structural and computational techniques can engineer and exploit unnatural protein–protein interfaces to design selective protein degraders.

Fast, single-molecule tracking microscopy monitors transitions between mobile and ribosome-bound fluorescent tRNAs to achieve nucleotide-resolution measurements of translation rates in living cells.

Variation in nutrient availability is a common challenge facing living organisms. Analysis of metabolomic and fluxomic responses in cyanobacteria to changes in nitrogen availability has led to the discovery of an ornithine–ammonia cycle.

Catalytic activity is a critical protein function, but its natural evolution has never been observed. Researchers have now revealed the mutations and biochemical mechanisms by which two ancient nonenzymatic proteins acquired catalytic activity.

Synthetic biology offers innovative approaches for engineering biological systems, but also supports the development of biocontainment strategies that ensure the safe application of genetically modified organisms.

Regulated destruction of proteins underlies just about everything a cell does. A structural study of human Gid4, the N-recognin of the Pro/N-end rule pathway that targets proteins through their N-terminal proline, illuminates the recognition of substrates by this proteolytic system.

Through molecular grafting, cyclic disulfide-rich peptides can be used as scaffolds to improve the stability, rigidity, and cellular uptake of bioactive peptides, although a number of factors should be considered when designing such grafted peptides.

Proteins brought to an E3 ubiquitin ligase are polyubiquitylated for rapid degradation via the proteasome. A new study developed a tag-based degradation system using heterobifunctional degradation inducers called dTAGs, which rapidly depleted FKBP12^F36V-fused proteins in cultured cells and in mice.

Targeting the host during antibiotic discovery efforts is a viable strategy, and the approach has benefited from phenotypic screening of model organisms such as worms, zebrafish, and mice.

Many thermodynamically unfavorable processes in biology are powered by ATP, the energy currency of the cell. New evidence suggests that chaperone-mediated protein stabilization may need to be added to that list.

Bioengineers have used directed evolution to generate a new family of synthetic transcription factors based on the tryptophan repressor. The evolved repressor family enables researchers to build new gene circuits for biomedical applications.

G-protein-coupled receptors (GPCRs) are critically involved in signal transduction. Structural views of several GPCRs have recently been obtained, but the structural principles determining subtype selectivity are still mostly elusive. Now, a combined solid-state NMR and molecular-modeling approach reveals how bradykinin GPCRs distinguish between closely related peptide ligands.

Technologies for engineering immune cells to recognize features on cancer cells are transforming oncology. Synthetic biologists now expand this approach by conferring therapeutic functions to nonimmune cells and by programming cells to sense and respond to a new class of physiological cues.

RNA structure is irrevocably linked to function. A new method, termed 'LASER', utilizes a light-activated chemical probe to query RNA tertiary structure and illuminate RNA–protein interactions in the living cell.

Early stages of protein evolution are inherently difficult to study. Genetic selection in Escherichia coli has now identified a life-sustaining de novo enzyme arising from a simple scaffold that is completely different from the native enzyme.