Articles

Adipose triglyceride lipase (ATGL), an enzyme in fatty acid metabolism, was identified as a negative regulator of the noncanonical inflammasome. ATGL binds to lipopolysaccharide and catalyzes the hydrolysis of fatty acid side chains blocking inflammasome activation.

A chemoproteomic method was developed that enables the global discovery of metal-binding proteins (MBPs) in proteomes, where the thermal stability of MBPs is perturbed by metal chelators. This tool, called METAL-TPP, is used to discover MBP candidates in the human proteome and provides a valuable method for functional annotation of MBPs in cell biology.

NinaB is an isomerooxygenase that generates visual chromophore (11-cis-retinal) from carotenoid substrates. Here Solano et al. reveal the structural basis for NinaB isomerase activity, providing new insights into the evolution of visual chromophore synthesis by carotenoid cleavage enzymes.

BURP-domain proteins are an unexplored family of plant-specific, copper-dependent peptide cyclases. Here the authors show that a BURP-domain protein has a particular protein fold, investigate its mechanism and provide evidence for intramolecular modification in RiPP biosynthesis.

Zhou et al. developed a specific small-molecule inhibitor of astrocytic Kir4.1 channels, Lys05, which exerts rapid-onset antidepressant effects in rodents without unwanted side effects, indicating Kir4.1 as a promising drug target.

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.

A disulfide tethering screen identified a molecule that covalently interacts with pro-apoptotic BAX at C126, inhibiting its activation.

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.