Articles in 2020

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.

We asked a collection of chemical biologists, “What is the most exciting frontier area in chemical biology and what key technology is needed to advance knowledge and applications in this area?” and reveal some of the perspectives we received.

This Review summarizes recent advances in CRISPR–Cas regulation mechanisms by natural biomolecules that enhance or inhibit CRIPSR–Cas immunity, as well as their applications in CRISPR biology and technologies.

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.

Rather than their expected role in self-immunity, kinases encoded in the biosynthetic gene clusters of nucleoside natural products catalyze the phosphorylation of an early intermediate, a modification that is later removed in a downstream step.

Insects have many ways of disabling plant chemical defenses during feeding. Plant phloem feeders use surplus ingested sugar to block the activation of glucosinolate toxins, providing a target for precise resistance breeding.

This themed issue features a collection of articles that explore long-standing questions in the study of lipids and membranes.

The conformational cycle of a bacterial voltage-gated sodium channel as it transitions from resting to activated open to inactivated closed states can be constructed from various crystal structure snapshots.

The authors report PROTAC ternary complex structures involving the E3 ligase cIAP1 and target protein BTK, showing that cooperativity is not always correlated with degradation efficiency.

The difficulty of antibiotic discovery posed by the double-membrane cell envelope of Gram-negative bacteria and active drug efflux requires better understanding of bacterial permeability and compound accumulation, and more diverse chemical libraries.

Ion channel structures reveal mechanisms of lipid action, including how channel gating is altered by direct binding of signaling lipids and those within the membrane itself, as well as mechanical and architectural effects of membrane lipids.

A proximity labeling strategy enables enrichment of cell type-selective secretomes in mice by direct biochemical purification of biotinylated polypeptides from blood plasma.

Qemistree uses fragmentation spectra to predict molecular fingerprints and represent their relationships as a tree, enabling comparison of metabolomics data across different experimental conditions and exploration of chemical diversity in mixtures.

Native mass spectrometry, HDX-MS and MD simulations define the mechanism for how LPS binding to the Gram-negative outer membrane complex LptDE opens the LptD lateral exit gate and how thanatin impairs transport across the periplasm.

The Hedgehog (Hh) receptor PTCH1 uses its transporter-like function to inhibit the GPCR SMO by limiting the pool of accessible membrane cholesterol. Cholesterol acts as a ligand for SMO to activate downstream signaling.

The asymmetric distribution of lipids, including cholesterol, in biological membranes established actively by flippases and scramblases has structural, biophysical and functional consequences in cells and implications for communication across membranes.

This Perspective highlights the evolution from the use of detergents to detergent-free membrane mimetics, as well as advances in structure determination and mass spectrometry that have allowed new insights into regulation and function of membrane proteins in native-like lipid environments.

The authors identify the interaction between transcription factor YY1 and DNA G4 structures, which contributes to chromatin looping induced by YY1 dimerization as well as its transcriptional regulation.

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.