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Single-molecule FRET sensors made by incorporating unnatural amino acids shed light on the mechanism of allosteric activation in mGluR2 metabotropic glutamate receptors, revealing how conformational changes of the ligand-binding domain with loose coupling to the cysteine-rich domain propagate during receptor activation.
The cumbersome encoding of digital data to cellular DNA hinders the use of cells as living hard drives. A new approach transfers digital information directly into cellular DNA by converting electrical signals into stable and interpretable changes in the genomes of bacterial populations.
A chemical screen identifies BET bromodomain inhibitors as inducers of an activated skin keratinocyte state that promotes the wound-healing capabilities of these cells. The study implicates epigenetic modifiers as potential targets for non-healing, chronic wounds.
This Perspective summarizes the recent advances in the structural diversity of amyloid fibrils and discusses the roles of post-translational modifications and chemical cofactors in the conformational determination of fibril polymorphs.
A new DNA data storage technology—data recording in vivo by electrical stimulation (DRIVES)—places CRISPR-based DNA encoding activity under electrochemical control by coupling cellular redox state to CRISPR array gene expression.
Crystal structures of FEM1C in apo and in complex with a C-degron ending with arginine reveal a binding pocket in FEM1C that recognizes C-degrons and the essential role of C-terminal arginine for recognition.
Using synthetic ubiquitins with non-natural acceptor site, the authors revealed that the length of lysine side chain in acceptor ubiquitins affects ubiquitin chain linkage specificity with native lysine as the preferred geometry.
A chemical screen identified BET bromodomain inhibitors as promoters of keratinocyte regenerative function and skin wound healing. Specifically, low-dose transient treatment with BET inhibitors imposes an activated, migratory state in keratinocytes.
Single-molecule FRET of mGluR2 shows that the conformations of the ligand-binding domain and the linked cysteine-rich domain are loosely coupled during ligand-induced activation and defines two pre-active states linking inactive and active states.
E3 ligase subunit protein Fbxo48 interacts with phosphorylated Ampkα and mediates its proteasomal degradation. Interruption of the pAmpkα/Fbxo48 interaction by a small-molecule BC1618 promoted Ampkα activation and improved insulin sensitivity.
A systems-based approach to profile glucocorticoid (GC) receptor ligands in a broad range of assays representing different phenotypic responses linked these to transcriptional profiles and led to separation of GC therapeutic effects from side effects.
Laboratory evolution of the bacterial transpeptidase sortase A coupled with yeast display selection enables a change of the enzyme’s substrate preference to recognize and covalently label endogenous amyloid-β protein, impeding the protein’s ability to aggregate.
Tryptolinamide (TLAM) is a small molecule compound that inhibits phosphofructokinase-1 activity and rescues the metabolic defects of patient-derived induced pluripotent stem cell lines with mutated mitochondrial DNA.
Unlike other amine oxidase-family enzymes, nicotine oxidoreductase (NicA2) reacts very slowly with oxygen, prompting the search for and identification of a cytochrome c protein (CycN) that is responsible for accepting electrons from NicA2 in vivo.
Coupling light-inducible bacterial biofilm formation with hydroxyapatite mineralization enables the synthesis of living patterned and gradient composite biomaterials with control over the degree of mineralization and the ability to self-heal.