Articles in 2021

Chimeric antigen receptor T cells (CAR-T cells) are often hindered by the concurrent challenges of variable antigen expression patterns and immunosuppressive tumor microenvironments. A new approach enhances CAR-T cells by coexpressing bacterial enzymes that activate prodrugs in high concentrations at the disease site.

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.

The Review summarized the recent progress in chemical probes and drug candidates for epigenetic writer enzymes and discussed the implication of targeting the chromatin regulatory landscape in cancer biology and therapy.

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–G_i 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.

Optogenetic and thermogenetic tools have been limited to applications for single-state control of cellular processes. A single-component optogenetic tool was found to act as both a temperature sensor and a photoreceptor, enabling multi-state control of developmental signaling.

Reliable quantification and tracing of RNA molecules remain challenging goals. A new fluorescent RNA tag, developed based on a natural adenine-sensing riboswitch and named Squash, offers superior imaging properties and accurate quantification in living 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 G_i 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.