Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin...

We report “Sirtuin Trapping Ligands” (SirTraps), mechanism-based 1,2,3-triazole inhibitors that hijack sirtuin (SIRT) catalysis to form covalent triazolium– or triazole–ADP-ribose (ADPR) adducts from...

imageimageMARUbylation (mono-ADP-ribose ubiquitylation) is a multilayered post-translational modification controlled by PARPs and Deltex E3 ligases. This study identifies RNF114 and RNF166 as reader-w...

MARUbylation is a hybrid post-translational protein modification in which mono-ADP-ribosylation acts as a scaffold for sequential mono- and polyubiquitylation. Recent studies illuminate its substrates...

The bacterial ubiquitin ligase NleL evades host defence mechanisms both by inhibiting pyroptosis and by preventing infected intestinal epithelial cells from being extruded into the lumen and expelled ...

Bacterial ATP-binding cassette (ABC) transporters can be utilized and engineered to transport non-canonical amino acids into Escherichia coli for highly efficient synthesis of proteins with novel func...

Stringent control of ubiquitylation is a central requirement of signaling specificity in eukaryotes. Here, we discover a domain module integrating pro…

Mitochondrial synthesis of adenosine triphosphate is essential for eukaryotic life but is dependent on the cooperation of two genomes: nuclear and mitochondrial DNA (mtDNA). mtDNA mutates ~15 times as...

Protein ubiquitination regulates cell biology through diverse avenues, from quality control-linked protein degradation to signaling functions such as modulating protein-protein interactions and enzyme...

Advances in mass spectrometry and associated computational tools have resulted in the wide-spread adoption of Data-Independent Acquisition (DIA) for proteomics. Experiments using state-of-the-art inst...

Li et al. discovered that the cytotoxic synthetic small molecule BRD1732 is directly ubiquitinated in cells. Ubiquitination of BRD1732 is E3 ligase dependent and leads to inhibition of proteasomal deg...

For life to emerge on Earth, peptides must first have formed without the aid of enzymes — but how? Reactions of sulfur-containing molecules might have been key.

Nature Communications - Ubiquitination is a versatile modification system in eukaryotic cells. Here, the authors unveil that the ubiquitin ligase HUWE1 can modify drug-like small-molecule...

The kinetochore fibrous corona docks on CENP-E and a second elusive receptor identified as the checkpoint protein BUB1.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

Append editing of ADP-ribosyl to thymine is used for precise modifications in bacteria and eukaryotes.

Depletion of a transcriptional factor ZBTB11 using molecular glue degraders can overcome oxidative-phosphorylation-mediated KRAS inhibitor resistance in pancreatic ductal adenocarcinoma with low acute...

Nature Chemistry - In living systems, ATP provides an energetic driving force for protein synthesis and modification. Now, an engineered enzymatic tool has been developed for high-yield, ATP-driven...

A preclinical covalent compound, CMX410, contains a aryl fluorosulfate warhead that targets the acyltransferase domain of Mtb Pks13, an essential enzyme in cell-wall biosynthesis, making it a pro...

Nature Chemical Biology - Glutarate rewires cell metabolism through conjugation to proteins or fatty acids, but how glutarylation is regulated is unclear. ABHD11 was identified as a...

Proteolysis-targeting chimeras (PROTACs) co-op the ubiquitin system for targeted protein degradation, creating opportunities to interrogate cellular functions of proteins through "chemical knockdown"....

Nardone et al. elucidate the mechanism of the midnolin-proteasome pathway, showing how midnolin achieves nuclear substrate selection and how established proteasomal components are repurposed to enable...

Nature Structural & Molecular Biology, Published online: 25 May 2025; doi:10.1038/s41594-025-01549-xCentrosomal protein assemblies can lead to mitotic spindle dysfunction and abnormal cell division. Two studies published in this issue unveil the molecular choreography orchestrated by TRIM37 in blocking the accumulation of these structures in a remarkable fashion that resembles viral capsid recognition.

Another reason why RFK Jrs. MAHA plan is misguided

Ubiquitin (Ub) cooperation with other post-translational modifications provides a tiered opportunity for protein regulation. Small modifications to Ub such as phosphorylation, acetylation, or ADP-ribo...

Liu et al. discover amide-forming enzymes in the biosynthesis of E-64, a classic cysteine protease inhibitor. Enzymatic combinatorial biocatalysis creates a large compound library and leads to the ide...

RNF213 is an E3 ligase with ATPase activity. Here, the authors show that RNF213 is activated by ATP binding and senses cellular energy states, and reveal a transthiolation mechanism induced by immune ...

Snake envenomation is a neglected tropical disease, with 600 species causing over 100,000 deaths and 300,000 permanent disabilities in humans annually…

Kazi et al. report the crystal structure of the mitochondrial deubiquitinase USP, a clinical stage Parkinson’s disease drug target, in complex with a specific inhibitor. The authors delineate a framew...

Ubiquitin-specific protease 8 (USP8) is a deubiquitinating enzyme with essential functions in protein trafficking and stability. It is a multidomain protein, with an N-terminal MIT (microtubule intera...

Nature - Molecular basis of SIFI activity in the integrated stress response

Kazi et al. report the crystal structure of the mitochondrial deubiquitinase USP, a clinical stage Parkinson’s disease drug target, in complex with a specific inhibitor. The authors delineate a framew...