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A mitochondria-activatable bioluminescent probe was designed enabling sensitive, non-invasive and longitudinal monitoring of mitochondrial membrane potential in vitro and in vivo.
The combination of heavy isotope labeling and ultra-high-pressure liquid chromatography coupled to triple-quadrupole mass spectrometry (UHPLC–MS) is used to quantify modified genomic cytosines in pluripotent stem cells in different states and reveals active turnover of methylcytidine in oxidation-dependent and oxidation-independent manners.
A PROTAC termed P4B targeting BRAF V600E mutant has been developed, which displays enhanced inhibitory function in cell lines carrying BRAF mutations that impart resistance to conventional BRAF inhibitors.
Levels of the endogenous bile acid cholic acid-7-sulfate (CA7S) increase in the gastrointestinal tract of both mice and humans after sleeve gastrectomy. CA7S acts through the G-protein-coupled receptor TGR5 to increase glucose tolerance during insulin resistance.
Chemical profiling in hyponeddylated cells coupled with multi-omics target deconvolution led to the identification of molecular glue degraders of cyclin K that function by inducing proximity between the CRL adaptor DDB1 and a CDK12–cyclin K complex.
The structural analysis of a covalent E2–E3 ubiquitin transfer intermediate reveals the ubiquitin relay mechanism via two Cys residues of E3 ligase MYCBP2, which is related to neurite growth and neurite protection phenotypes.
An orthogonal O-glycan biosynthesis system was engineered in Escherichia coli to support the production of glycoproteins displaying human mucin O-glycans, including Tn antigens, in living bacteria and in cell-free extracts.
TAp63α monitors the genome integrity in oocytes. After DNA damage, TAp63α is activated, involving multiple phosphorylation steps by CK1 with different kinetics due to an unusual CK1/TAp63α interaction in which the product of one step inhibits the next.
Biocatalytic cascade reactions using engineered variants of ferulic acid decarboxylase coupled to carboxylic acid reductase utilize carbon dioxide fixation to enable the carboxylation and functionalization of styrene and other aromatic compounds.
A robust mass spectrometry workflow was developed for rapid drug perturbation profiling in multiple cell lines, enabling improved mechanistic deconvolution of single compounds and revealing novel mechanisms of action.
Highly selective activators of IRE1/XBP1 splicing pathway were identified via high-throughput screen, which promoted the degradation of APP and reduced APP-associated mitochondrial toxicity in an IRE1-dependent manner.
TH1760 is a first-in-class, potent, selective and cell-active inhibitor against human NUDT15, which sensitizes cells to 6-thioguanine treatment. TH1760 represents a valuable tool for deciphering the enigmatic functions of NUDT15.
A new ligand against the GPCR GLP-1R acts as a positive allosteric modulator, binding both the receptor and the orthosteric ligand, accessing the peptide ligand within the interface between transmembrane domains 1 and 2 of the receptor.
A method combining multiplexed genome engineering, genetic code expansion and biorthogonal chemical labeling has been developed for multiple site-specific protein labeling and used to label ribosome components at sites hard to access for FRET assays.
Engineering cleavage sites into gas vesicle proteins enables protease-responsive regulation of gas vesicle mechanics and activates them as ultrasound contrast agents for imaging applications in cells and living mice.
An econometric model built on regulatory networks and calibrated by proteomics data identifies nonessential transcription factors that when deleted in Escherichia coli result in a strain with an expanded proteome for engineering applications.
A synthetic phase separation system consisting of two protein components with tunable parameters was developed to visualize and characterize phase diagrams in living cells, revealing that increasing the interaction affinity enhances phase separation and the viscosity of condensates in vivo.
Characterization of the interaction between PTH and its G-protein-coupled receptor, PTHR, shows conformational changes coupled to residues interacting with His9, which helps position the PTH N terminus at the PTHR transmembrane domain to facilitate β-arrestin coupling.
Structural, conformational and biochemical characterization of the AROM complex and its constituent shikimate pathway domains reveals how the complex balances compactness and conformational freedom, yet does not benefit from substrate channeling.
