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Neutrophil granulocytes can fight microbes either by phagocytosis or by formation of neutrophil extracellular traps (NETs), an extracellular structure that captures and kills bacteria, fungi and parasites. Using a chemical genetics approach, Hakkim et al. identified the Raf-MEK-ERK signaling system downstream of PKC in formation of NETs. The cover image shows a group of neutrophils that have developed NETs (yellow) after contact with Shigella flexneri bacteria (blue). Cover art by Erin Dewalt, based on an image from Volker Brinkmann. Article, p75
Monoubiquitylation of histone H2B is found to disrupt condensation of chemically defined chromatin fibers. A novel fluorescence-based assay is used in concert with analytical ultracentrifugation to uncover the synergistic roles of histone acetylation and ubiquitylation on chromatin dynamics.
The vast majority of core structures of protein and peptide glycosylation motifs belong to either O-linked or N-linked glycans. A recent publication describes the structure and biosynthesis of an unusual S-linked glycan linkage in the antibacterial glycopeptide sublancin.
The development of small-molecule probes for use in neural stem cells demonstrates the importance of endogenous ROS signaling in regulating in vivo phenotypes.
A new quantitative proteomic approach can identify reactive cysteine residues in native proteins and distinguish them on the basis of reactivity. This resource-rich study offers a useful new technology and is a significant step toward understanding the reactivity and functions of cysteines in cells.
A chemical genetics approach identifies the Raf-MEK-ERK signaling system downstream of PKC in formation of the antimicrobial cell structures called neutrophil extracellular traps.
The structural revision of sublancin, previously thought to be a lantibiotic, instead reveals an unusual S-linked carbohydrate that is installed by a glycosyl transferase specific for thiols but promiscuous in its sugar substrates.
Biomimetic divalent ligands based on the PDZ domain–binding motifs from the AMPA receptor auxiliary subunit Stargazin disrupt the receptor's interaction with the scaffold protein PSD-95 and show that AMPARs are stabilized at synapses by engaging in multivalent interactions with PDZ domain-containing proteins.
Identifying the cellular targets of small molecules remains a central challenge of chemical biology. The application of an RNAi-based functional genomics approach permitted the clustering of drugs with related targets by 'shRNA signatures', which served as a basis set to assign modes of action to compounds with unknown targets.
Numerous aerobic bacteria depend on glutathione but are lacking the first enzyme in its biosynthetic pathway. An evolutionary experiment identifies a likely natural route to compensate for this loss through mutations in two enzymes in proline biosynthesis.
A new fluorescent indicator reveals that a ROS-producing NADPH oxidase generates H2O2, normally associated with pathological conditions such as neurodegeneration, in neural stem cells where it regulates Akt phosphorylation and normal cell proliferation.
Ubiquitylated histone H2B (uH2B) is a known chromatin modification involved in transcription. Analysis of nucleosome arrays containing chemically synthesized uH2B proteins revealed that this posttranslational modification impairs chromatin fiber compaction and increases its accessibility through a mechanism distinct from other chromatin marks.
Random and targeted mutagenesis of serum paraoxonase, coupled with the development of a screen that allows detection of enzymatic activity against the toxic isomer of cyclosarin, yielded a mutant enzyme capable of protecting mice from a lethal dose of this dangerous nerve agent.