A multiscale photoproximity labeling proteomics workflow captures dynamic neighborhoods of extracellular and intracellular epidermal growth factor (EGF) receptor interactomes during early, middle and ...

Nitrogen fixation by nitrogenase requires a metallocofactor built by a dedicated multiprotein machinery. Here, the authors captured structural snapshots of a precursor entering a key maturase, reveali...

Degrons are degradation signals in target proteins to direct recognition and degradation by the ubiquitin–proteasome system. Wang et al. introduce degrons of different types, with an emphasis on high-...

Marine sponges host bacteria that produce diverse bioactive compounds. Here, the authors conduct a large-scale metagenomic, single-bacterial and biochemical study to reveal the untapped biosynthetic p...

This Perspective discusses how elevated-temperature crystallography uncovers hidden dynamic states of protein, ligand and water molecules, expanding insights into the protein conformational landscape ...

Performing live-cell microscopy experiments with high spatial and temporal resolution requires fluorophores with highly optimized properties. This Review examines the progress in developing synthetic ...

Exploiting the high abundance of mutant p53 protein, a small molecule was developed that specifically binds to p53-Y220C mutants and delivers a mitosis blocker, killing TP53-mutant cancer cells while ...

By mapping oxidatively damaged bases and abasic sites at single-nucleotide resolution in human cells, Takhaveev et al. observed transcription-related strand biases, patterns mirroring cancer mutationa...

Microbial alcohol production from waste gases could enable sustainable carbon cycling. Now, the tungsten-dependent aldehyde:ferredoxin oxidoreductase from the gas-converting bacterium Clostridium auto...

SIRT1-driven deacetylation of the MED1 subunit of the Mediator complex under stress modifies gene expression by enhancing RNA polymerase II action, promoting survival and growth of estrogen-receptor-p...

Hydrogen exchange–mass spectrometry (HX–MS) is used to qualitatively assess how perturbations such as mutations and ligand binding impact protein ensembles. However, in theory, HX–MS data contain the ...

Phenotypic screening of an endophyte-derived compound library led to identification of a potent anti-non-small cell lung cancer (NSCLC) lead compound, the 3,4-diisobutyryl derivative of auxarthrol A, ...

This Review discusses recent strategies for integrating microbial metabolism with chemocatalysis, electrocatalysis, photocatalysis and biocatalysis to enable sustainable chemical production. By highli...

Duan and Kaushik et al. reveal the structural basis of how Escherichia coli and Thermus thermophilus RNA polymerases initiate transcription from Np4A alarmones producing Np4-capped transcripts. The ca...

Zhu, Fu, Zhu, Li and colleagues found that the key DNA repair enzyme poly(ADP-ribose) polymerase 1 promotes transcriptional restart after DNA damage through PARylating and stabilizing AFF1 by preventing its ubiquitylation by the E3 ligase Siah1.

This study presents prime-editing-based inversion with enhanced performance, a prime editing-based system that enables efficient and precise genomic inversions from kilobase to chromosome scale, offering a powerful tool for chromosomal engineering, disease modeling and studying three-dimensional genome architecture.

In plants, oxidosqualene cyclases (OSCs) perform a highly complex single reaction to generate the basis of all triterpenoid diversity. Here the authors leverage genome mining and transient expression to uncover multiple evolutionary and mechanistic insights for OSCs across the plant kingdom.

This Review explores how post-translational modifications orchestrate replication stress responses by regulating checkpoint signaling, DNA repair and fork remodeling, thereby preserving genome stability under genotoxic conditions.

Engineered aminoacyl-tRNA synthetase (aaRS) mutants have been developed that facilitate ultrafast bioorthogonal noncanonical amino acid tagging (BONCAT) of newly synthesized proteins in diverse bacteria, including ESKAPE pathogens. The substrate polyspecificity of the aaRS mutants enables pulse-chase BONCAT and differential tagging of temporally distinct nascent proteomes in cells.

Low-antigen-expressing cancers are a challenge to existing chimeric antigen receptor (CAR)-T cell-based therapies. Now, it has been shown that fusion of intrinsically disordered regions to CARs induces CAR condensation and enhances antigen sensitivity and killing activity of CAR-T cells.

Static protein structures can capture the association of lipids, but it is unclear whether the association is due to lipids acting as long-lived ligands or the solvation of preferred lipids around the protein. A computational-experimental framework has now shown that for the protein CLC-ec1, it is the change in lipid solvation energies that drives dimerization, with preferred lipids around the protein modulating this driving force.