Research articles

Cryo-EM structure and dynamics analysis provides a conformational mechanism for tuning of selectivity between calcitonin and amylin receptors through targeted lipid modification of residues 19–22 within the ‘bypass’ motif of amylin peptides.

Asymmetric glucose tracers reveal the simultaneous use and unique benefits of parallel glycolytic pathways. Cells possessing both textbook glycolysis and Entner–Doudoroff glycolysis have a selective advantage in dynamic environments.

Altering the biophysical positioning of endosomes reveals a regulatory mechanism underlying location-biased responses for G-protein-coupled receptors (GPCR)/cyclic AMP (cAMP)-dependent signaling.

Enolase 1 (ENO1) is a critical glycolytic enzyme that plays essential roles in pathological activities. Here, Sun, Suo, Zhang, Shen et al. reveal the nonmetabolic function of ENO1 in liver cancer, where ENO1 promotes YAP1 mRNA translation to activate arachidonic acid metabolism thus promoting cancer growth.

A pivotal role for beta-1 adrenergic receptor (β1AR) subcellular signaling in controlling cardiac relaxation response through the generation of cyclic adenosine monophosphate (cAMP) and activation of local protein kinase A (PKA) effectors was revealed in cardiomyocytes and in intact zebrafish and mice hearts.

Three-dimensional imaging reveals the existence of GPCR domains at the plasma membrane of living cells. The molecular mechanism underlying this spatial organization is energetic coupling of receptors to the curvature of the plasma membrane.

Tian et al. developed a bacterial orthogonal DNA replication system by harnessing the temperate phage GIL16 DNA replication machinery, which provides a powerful tool for continuous evolution in prokaryotic cells.

A probe for the ubiquitin-like protein Fubi led to the discovery of dual ubiquitin/Fubi C-terminal hydrolase activity in the deubiquitinase USP16 in addition to USP36, enabling structural characterization of this distinctive Ub/Ubl specificity, and revealed a synergistic role of USP16 in ribosomal protein maturation.

Synthetic cells, modular gene-expressing compartments, have shown promising applications in biology and medicine; however, more diverse tools are required for their control and communication. Now, photocaged promoters and cell-free synthesis of an acyl homoserine lactone have been used to demonstrate light-activated communication between synthetic cells and living cells.

Phage and yeast display were used to generate variable heavy single-domain antibodies that bind and allosterically inhibit ectodomain phosphatase/phosphodiesterase-1 to increase the half-life of the immune-stimulant cyclic guanosine monophosphate adenosine monophosphate (cGAMP) in tumor microenvironments.

Tao et al. reported a series of cryo-EM structures of α-synuclein fibrils in complex with amyloid dyes and imaging tracers, and identified druggable pockets in the fibrils of multiple system atrophy.

Wu, Liu, Zou et al. report an engineered hypercompact AsCas12f system, enAsCas12f, for robust and faithful genome editing in human cells. Cryo-EM study validates the engineering strategy and reveals dimerization-based substrate recognition by AsCas12f.

Wang et al. discovered that many cancer-causing fusion proteins form abnormal condensates that affect gene expression and developed a kinetics-dependent screening method called DropScan to find drugs that can dissolve the abnormal condensates to restore normal gene expression.

The secreted aminopeptidase Pseudomonas aeruginosa aminopeptidase (PaAP) is required for nutrient recycling in biofilms. Using the information from protein structure and kinetics, a potent cyclic peptide inhibitor for PaAP was designed that killed cells in late-stage biofilms.

Genetic and bioorthogonal chemistry approaches reveal cell-to-cell movement of brassinosteroid (BR) hormones via plasmodesmata in plants. In turn, BRs positively regulate callose deposition at plasmodesmata to balance its own biosynthesis.

Engineering of a focal adhesion kinase (FAK) reporter that visualizes endogenous FAK activity with dynamic spatiotemporal resolution in living cells and vertebrates reveals tension-induced polarized FAK activity in single focal adhesions during cell migration.

Seo and Kleiner developed a small-molecule-dependent RNA editing platform termed TRIBE-ID to profile RNA–protein interactions in cells with temporal control and to study substrates of the stress granule protein G3BP1 during biomolecular condensation.

Bioinformatic and chemoproteomic approaches resulted in the identification of a homolog of human dipeptidyl peptidase 4 in the gut bacterium Bacteroides thetaiotaomicron that regulates envelope integrity and community fitness.

A carbon nanotube-based sensor was developed to monitor endolysosomal acidification events in live cells and in vivo. The technology enables a spatiotemporal measurement of endolysosomal pH and real-time tracking of the dynamics of autophagy in tumors.

A chemoproteomic approach is developed that examines changes in ligand binding-induced accessibility by globally labeling reactive proteinaceous lysines, revealing the cellular targets of glycolytic intermediates.