Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
α-Synuclein and tau can form multiple amyloid structures or strains that are associated with different neurodegenerative diseases, suggesting a strain–toxicity relationship. Now, it has been shown that O-GlcNAc modification of α-synuclein results in the formation of an amyloid strain that is largely nonpathogenic in vivo, supporting structure-dependent toxicity and another protective role for O-GlcNAc.
Tong et al. engineered Cas12b and redesigned the target sequence of Cas13a to minimize the interference caused by the cleavage mediated by Cas effectors in one-pot testing, which enables sensitive nucleic acid detection in a simple way at room temperature.
SUGAR-TARGET is a modular platform for the homogeneous synthesis of enzymes with controlled N-linked glycosylation using a one-step immobilization/purification method.
Nonribosomal peptide synthetases produce valuable natural products but are challenging to engineer. Yeast surface display and fluorescence-activated cell sorting have now been combined to reprogram a condensation domain to recognize a noncanonical lipid substrate. This methodology may facilitate molecular tailoring of many biosynthetic assembly lines.
Unbiased antibody discovery identified allosteric regulators of PAD4, revealing mechanisms to alter PAD4’s activity and providing tools to study rheumatoid arthritis.
Hao et al. developed a method termed RNA editing-mediated noncanonical amino acids protein tagging (RENAPT), which combines RNA editing and genetic code expansion techniques to label endogenous proteins for real-time imaging in living cells.
Metabolome-informed proteome imaging provides a comprehensive view of underlying biological pathways within micrometer-scale microhabitats of the fungal garden, informing the understanding of metabolic fungal pathways in plant matter degradation.
Platelet-activating factor (PAF) and PAF-like phospholipids were identified as propagators of ferroptosis, whereas PAFAH2 suppressed synchronized ferroptosis and, thus, prevented tubular cell death in acute kidney injury.
Vaccine immunoadjuvants are central to vaccine efficiency. Now, the complete characterization of the biosynthetic pathway of QS-21, a potent immunoadjuvant produced by the Chilean soapbark tree, has been reported. These findings open the door to heterologous production of QS-21 and new-to-nature adjuvants.
The plant AUG-stop element in the 5′ UTR acts as a boron concentration sensor, regulating downstream ORF translation. Here, structural and biochemical analyses show that a high concentration of borate fixes eRF1 on 80S ribosomes, preventing sliding through downstream of AUG-stop elements.
The authors determined a set of structures of the methylase Cfr-methylated 70S ribosome with iboxamycin and tylosin, two antibiotics that evade Cfr-mediated drug resistance, and revealed two distinct mechanisms by which small molecules can maintain their ability to engage the Cfr-methylated ribosome.
Hanswillemenke, Hofacker and colleagues developed a proximity labeling-based method to identify protein interactome of small molecules and RNA drugs within living cells, facilitating the design and development of RNA drugs with enhanced pharmacological properties.
A new design for vaccines consisting of reorienting the viral glycoprotein in an ‘upside-down’ configuration broadens immune responses to diverse influenza subtypes and serves as a proof of concept for designing a universal flu vaccine.
A small molecule, CGI1746, was identified to block ferroptosis acting through the sigma-1 receptor, a chaperone primarily at endoplasmic reticulum–mitochondria contacts to mediate calcium transfer.
Qin et al. find that cell detachment induces condensation of LATS2, a core kinase of the Hippo pathway. These LATS2 condensates protect LATS2 from degradation by the ubiquitin–proteasome system, thereby promoting the assembly of Hippo signalosomes for pathway activation.
Integrated chemoproteomic development of selective small-molecule SLC15A4 inhibitors and their functional characterization establish SLC15A4 as a druggable target for autoimmune conditions.
Hernandez-Candia et al. introduce BTBolig, a chemical-based tool to manipulate biomolecular condensates, and CoSMo, a method for control of condensate maturation. When used together, the authors observe dynamic interactions of condensates with protein chaperones.
The small molecule SRI-41315 induces the degradation of the translation termination factor eRF1 to enhance stop codon readthrough. Coelho, Yip et al. reveal that SRI-41315 is a metal-dependent molecular glue that traps eRF1 on terminating ribosomes.
Identification of a small molecule (Ebio1) reveals a unique activation mechanism for the KCNQ2 potassium channel. Ebio1 induces a twist-to-open movement in the S6 helices, creating an extended channel gate with enhanced conductance.