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Elucidation of the bacterial ceramide biosynthetic pathway reveals that it likely evolved independently from the eukaryotic pathway, as bacteria lack homologs for many of the eukaryotic enzymes and the reactions occur in a different order.
The synthetic enzyme-armed killer (SEAKER) approach equips chimeric antigen receptor (CAR)-T cells with the capacity to express enzymes that process anticancer prodrugs at tumor sites of action.
IsoAnalyst is a mass spectrometry-based parallel stable isotope labeling platform that associates labeling patterns with bioinformatic structure prediction in order to connect natural products to their corresponding biosynthetic gene clusters.
Engineering of a bacterial-derived retron system enhances production of reverse-transcribed DNA for genome-editing applications in bacteria, yeast and human cells.
Cryo-EM structures of the CCR1–Gi complex with N-terminal truncations of the endogenous chemokine CCL15 revealed that the conformational change of Tyr291 in CCR1 regulates β-arrestin signaling.
A genome-wide CRISPR screen revealed that loss of general control nonderepressible 2 (GCN2) kinase increases cellular resistance to the pan-ErbB inhibitor neratinib with neratinib directly binding and activating GCN2 kinase activity.
A computational pipeline linking molecular dynamics simulations and an elastic network model-based method identifies druggable sites in the parathyroid hormone class B GPCR and a nonpeptidic allosteric modulator of receptor signaling in cells.
The adenine riboswitch was evolved into a fluorogenic aptamer by randomizing the sequence and size of the ligand-binding pocket. The resulting fluorogenic aptamer, Squash, is highly folded and was adapted for ratiometric live imaging of SAM.
Structural characterization and fluorogenic screening of a hydroxylase–halogenase chimera library enable switching of a hydroxylase into a robust and selective halogenase.
Cryo-EM structures of sphingosine-1-phosphate receptor with Gi bound and in complex with ligands revealed the key conformations and interactions that mediate β-arrestin bias.
The BcLOV4 photoreceptor was used to generate single-component optogenetic signaling probes whose activation dynamics are dependent on light and temperature, allowing multiplexing of blue-light-sensitive tools in mammalian cells
Cryo-EM and molecular dynamics simulation analysis of peptide variants of GLP-1 and exendin-4 reveal distinct receptor conformers with unique modes of peptide–receptor engagement.
Truong et al. report crystal structures of Squash, a fluorophore-activating aptamer RNA evolved from the adenine riboswitch. Squash preserves the overall scaffold of the adenine riboswitch, yet has a highly divergent ligand-binding site.
The agrochemical mandipropamid (Mandi), which induces dimerization of a variant of the abscisic acid receptor, has been developed as a new chemical inducer of proximity for cellular and organismal applications.
Bacterial populations, programmed to self-assemble by adhesion of nanobody–antigen pairs, can be processed into living materials (LAMBA) that are scalable, self-healing and programmable through functionalization with diverse proteins.
Biochemical and structural characterization of a homozygous point mutation in the GPX4 gene (R152H) reveals loss of enzymatic function and resistance to degradation. Therapeutic treatments such as selective antioxidants can overcome R152H defects.
Structures of the bifunctional heme transporter cytochrome c synthase CcsBA in closed and open states show how heme binding in the periplasmic site induces a conformational shift, exposing the heme and facilitating its transfer to apocytochrome c.
In Bacillus subtilis, glutamate synthase (GltAB) and glutamate dehydrogenase (GudB) catalyze opposite reactions that synthesize and break down glutamate, respectively, and form a regulatory complex to inhibit GudB under glutamate-limited conditions.
Cryo-EM analysis with DEER spectroscopy and molecular dynamics simulations of the ABC exporter BmrCD reveal dual-mode substrate binding in an ATP- and substrate-bound state.
With the example of the paraspeckle protein PSPC1, Shao et al. demonstrated the synergistic interplay of promoter-associated RNA and its binding proteins in promoting transcription condensate formation and Pol II engagement and activity via phase separation.