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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.
Macromolecules can undergo liquid–liquid phase separation to form condensates that have critical roles in biological functions and dysfunctions. A new study demonstrates that differences in micropolarity between components is a prime determinant of the multiphasic architecture of biomolecular condensates.
Half a century after its discovery, platelet-activating factor (PAF) is now recognized as a ferroptosis-activating phospholipid that contributes to tubule cell damage and nephron loss in acute kidney injury.
SUGAR-TARGET is a modular platform for the homogeneous synthesis of enzymes with controlled N-linked glycosylation using a one-step immobilization/purification method.
Developing therapeutic agents that target the peptidylarginine deiminase PAD4 requires better understanding of the function of the enzyme. Isozyme-selective antibodies that alter PAD4 activity have been identified recently, revealing unique modes of action.
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.
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.