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Unbiased antibody discovery identified allosteric regulators of PAD4, revealing mechanisms to alter PAD4’s activity and providing tools to study rheumatoid arthritis.
A second-timescale optogenetic strategy DeKinomics was developed, enabling the study of downstream events of kinases in a gain-of-function manner. Using this technique, UBA1, an E1 enzyme that initiates the ubiquitination cascade, was found to be directly regulated by tyrosine phosphorylation.
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.
SRI-41315 is a small molecule that enhances premature read-through of the stop codon by triggering the degradation of the translation termination factor eRF1. Cryo-EM structures and biochemical analyses reveal how SRI-41315 acts as a molecular glue between eRF1 and the decoding center of ribosomes, leading to increased recognition of the cryptic stop codon and eRF1 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 K+ ion channel KCNQ2 modulates neuronal excitability and is targeted by retigabine, an anti-epileptic drug that enhances the probability of channel opening. New activators have now been discovered to increase unitary conductance through an unprecedented mechanism.
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 rules for designing cyclic peptides with drug-like properties are unclear. Two studies now show how cyclic peptide libraries can be created to optimize properties such as cell permeability before screening for binding activity. The approach has led to a macrocyclic peptide inhibitor for KRAS that has reached clinical trials.
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.
Sirtuins remove post-translationally added acyl groups from protein lysines. New work shows the surprising metabolic fate of acyl groups removed from mitochondrial proteins—they react nonenzymatically with essential polyamine spermidine, forming previously unknown monoacylated N-glutarylspermidines and diacylated N-glutaryl,N-acetylspermidines.
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.
