Browse Articles

The role of lipid membrane domains in the activation of immune cells remains elusive. New microscopy data on B cell signaling support a mechanism in which lipid membrane domains consolidate upon B cell receptor clustering.

Super-resolution imaging detects plasma membrane domains that emerge when receptors are clustered in live B cells. Domain structures arise due to the membrane phase transition and can tune local membrane organization and receptor activation.

Pseudouridine (Ψ) is an important modification in RNA biology and mRNA vaccine. A method called PRAISE was developed via selective labeling of Ψ by bisulfite to induce nucleotide deletion signature during reverse transcription, thus realizing quantitative assessment of the Ψ landscape in the human transcriptome.

Koller et al. determined structures of the O-glycosylated antimicrobial peptide drosocin from Drosophila melanogaster in complex with the bacterial ribosome, revealing the mechanism by which drosocin inhibits the termination phase of protein synthesis.

The antimicrobial peptide Drosocin encoded in the fruit fly genome inhibits bacterial translation by stalling the ribosomes at stop codons, sequestering class 1 release factors and inducing stop codon readthrough. Comprehensive mutational analysis reveals key activity determinants of Drosocin.

A study of drug-resistant lymphomas with hypermorphic mutations in PRC2 has identified a ‘methylation index’ by which cancer cells maintain optimal H3K27me3 levels for survival, emphasizing the importance of understanding how tumors adapt to changes in chromatin and to drug-resistance mutations.

The NADP⁺/NADPH coenzyme couple powers cellular biosynthesis and oxidative defense. A new study tracing glucose-derived deuterium during proline biosynthesis analyzes subcellular perturbations in NADPH utilization, revealing that NADP⁺/NADPH coenzyme pools in the cytosol and mitochondria are regulated independently.

Biased signaling gives hormones, probes or drugs distinct functional outcomes via the same receptor. The Biased Signaling Atlas (https://BiasedSignalingAtlas.org) provides a community hub with data and tools to advance this paradigm, which may yield safer and more potent drugs.

Profiling the resistance landscape to PRC2 inhibitors in EZH2-mutant lymphoma with CRISPR-suppressor scanning reveals drug addiction mutations and a repressive methylation ceiling. Surpassing the ceiling with SETD2 inhibition halts lymphoma growth.

An approach using glucose tracers and labeling of proline metabolites is applied to assess compartmentalized NADPH fluxes. The results show that NADPH fluxes in the cytosol and mitochondria are independently regulated, with no evidence of a shuttle.

Zhu et al. show how the growth-rate-dependent gene expression reshapes the landscape of cell-fate determination and highlight that expression capacities of genes have unbalanced response to growth variations.

Identifying new proteoforms — structural variants of proteins — is frequently challenging, particularly on the proteome-wide scale. A new study leverages their differential thermal stabilities to identify proteoform functional groups by deep thermal proteome profiling.

Applying thermal proteome profiling to acute B cell childhood leukemia cell lines combined with deep peptide fractionation and a graph-based clustering algorithm allows inference of functional proteoform groups and their association with drug response.

A new review article details how new structural insight regarding modular polyketide synthases (PKSs) helps us better understand the organization of catalytic events within a PKS module. The plausible models discussed will likely influence future PKS engineering efforts.