The fusion of egg and sperm requires an egg surface protein, JUNO in mammals or Bouncer in fish, and several conserved sperm surface proteins, including IZUMO1, SPACA6, DCST1 and DCST2. The binding of JUNO and IZUMO1 is known but is not sufficient for fusion, and the specific roles of SPACA6 and DCST1/DCST2 remain unclear. Deneke, Blaha et al. have now identified a conserved sperm complex that includes

The aberrant aggregation of the presynaptic protein α-synuclein (α-syn) is a hallmark of synucleinopathies, which include Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Previous studies have suggested that α-syn can undergo liquid–liquid phase separation (LLPS) and transition from a liquid to a solid state, which contributes to aggregation and fibril formation. However

Forkhead box protein A1 (FOXA1) is a pioneer transcription factor that binds to chromatin at a canonical DNA motif. This binding promotes the opening of chromatin, providing access to additional transcription factors. Targeting transcription factors such as FOXA1 with small molecules can serve as a useful tool to elucidate the rapid dynamics of transcriptional regulation, but remains difficult owing

Correction to: Nature Chemical Biology https://doi.org/10.1038/s41589-022-01102-7, published online 22 August 2022.

Correction to: Nature Chemical Biology https://doi.org/10.1038/s41589-024-01759-2, published online 14 October 2024.

Targeted protein degradation has emerged as a highly promising therapeutic approach to modulate proteins that are difficult to target with conventional small molecules. This approach has recently been expanded to include alteration of extracellular protein levels and activity — including both secreted and membrane proteins. Now, Zhang et al. have exploited the upregulation of cell surface transferrin

Folates are a group of water-soluble B vitamins that are essential for all organisms. Although plants and microbes can synthesize them, humans cannot, and insufficient intake of folates can lead to several disorders. It is therefore important to find folate sources that can help alleviate folate malnutrition. Cereals are poor sources of folates but contain high levels of MeFox, a pyrazino-s-triazine

Early-onset Parkinson’s disease (EOPD) is a movement disorder caused by loss of specific neurons in the midbrain that are responsible for fine motor control. Mutations in the ubiquitin ligase parkin and the kinase PINK1 (which work together to target degradation of damaged mitochondria) cause EOPD, as mitochondrial homeostasis is crucial for neuronal survival. Upon mitochondrial damage, PINK1 accumulates

Enzymes efficiently catalyze numerous reactions, but re-engineering them to speed up reactions that are not known in nature is challenging. Lanthanides, particularly cerium complexes, have previously been used in photocatalytic transformations that proceed via radical species. However, these radical reactions are rarely stereoselective. In an effort to address this, Klein, Leiss-Maier et al. developed

Biomolecular condensates perform their cellular functions via the exclusion or enrichment of molecules. Analyzing the composition of condensates is important for understanding their properties and functions. A considerable amount of work has gone into understanding the nucleic acid and protein components of condensates; however, much less is known about partitioning of small molecules and the determinants

Mitochondria have a crucial role in replenishing ATP, the molecule used to provide cellular energy. This is achieved by tightly coupling the movement of protons (H+) across the inner mitochondrial membrane to power the rotary action of ATP synthase in the final step of oxidative phosphorylation. Folds of the inner mitochondrial membrane called cristae provide a large, ion-impermeable surface area studded

Research in the early days of chemical biology was mostly limited to the application of chemical tools to model cell lines grown in incubators. Now, discoveries are being made in more physiologically relevant systems, from tissues to organisms, using precisely targeted molecules. The 2023 Chemical Biology & Physiology meeting (in Portland, Oregon) discussed the latest advances in the field, with research

N-acetyltaurine is a metabolite whose levels fluctuate with diet and exercise and that undergoes hydrolysis to form taurine and acetate. However, the enzymes that facilitate this reaction were not known. In an effort to address this, Wei et al. used liquid chromatography–mass spectrometry-based activity guided analysis of mouse tissues, detecting high N-acetyltaurine hydrolysis activity in kidney and

The formation of pathological protein aggregates occurs in many neurodegenerative diseases, such as the aggregation of the protein tau in patients with Alzheimer’s disease. Removing these aggregates offers a possible route to treat these protein misfolding diseases; however, targeting the aggregated form of a protein while sparing the monomeric form, which is required for normal cellular function,

By coupling rPAL to enzymatic glycan cleavage and sequential window acquisition of all theoretical mass spectra (SWATH-MS), the team found that acp3U was the most enriched linker (although other putative linker substrates were identified). Importantly, knocking out DTWD2, an enzyme responsible for installing acp3U in tRNAs, reduced glycoRNA levels. This study provides not only a useful tool for glycoRNA