Reviews & Analysis

Lytic polysaccharide mono-oxygenases oxidatively cleave the glycosidic chain on the crystalline surface of cellulose or chitin to create an entry point for hydrolytic cellulases or chitinases. The discovery of a new family of lytic polysaccharide mono-oxygenases expands the possibilities for the use of these enzymes to accelerate biomass degradation.

Altered glycosylation of cancer cells confers phenotypic changes that promote spread and evasion of immune responses. A new method for engineering cell surface glycans is providing insights into these mechanisms.

Iron is essential for biological systems but can also damage or kill cells, leading to a variety of disease states. A review of mechanisms leading to Fe- and ROS-dependent cell death highlights the vast array of open questions in this complex field.

A highly original and sensitive method using clickable bioorthogonal fatty acids and in situ proximity ligation enables the visualization of the palmitoylation of not only Wnt but also its fatty acyltransferase Porcupine in cells.

Advances in genome sequencing and structural biology mean that we are now buried under an avalanche of predicted domains and structures of proteins with unknown functions. Two groups have used different methods to unearth the functions of previously cryptic bacterial enzymes, illuminating new reactions and metabolic pathways.

Allergic reactions to otherwise innocuous substances involve a complex interplay of molecular interactions—some strong, some weak. This study reveals a key role for low-affinity antibodies and thus a possible point of weakness that may be exploited for therapeutic intervention.

Noncanonical translation of prespliced mRNA provides physiological meaning to nuclear translation in generating antigenic peptide substrates for the endogenous major histocompatibility complex class I pathway.

The Doc-Phd pair forms a bacterial toxin-antitoxin system, but the mechanism by which the Fic-family member Doc causes toxicity is not fully defined. New research shows that Doc unexpectedly functions as a kinase to phosphorylate elongation factor TU, thus inhibiting translation and leading to Doc-mediated growth arrest.

Large-scale cell line profiling of drugs provides dose-response curves that contain numerous lesser-considered parameters. Understanding the reasons for systematic variation in these parameters offers new ways to compare drugs and potentially to guide improved drug profiles.

NAD⁺-dependent deacetylases of the sirtuin family have long been implicated in lifespan regulation, and the significance and molecular mechanism (or mechanisms) of this effect have engendered spirited debate. Two articles now spotlight the catabolism of NAD⁺ itself as a mediator of lifespan regulation.

The nicotinic acetylcholine receptor (nAChR) is regulated by changes in the host lipid bilayer composition and has been studied extensively to elucidate the relative importance of specific lipid-protein interactions versus more general nonspecific bilayer-protein interactions in the regulation of membrane protein function. Experiments reported in this issue provide strong support for the importance of lipid bilayer physical properties and lipid bilayer–membrane protein hydrophobic mismatch in the regulation of nAChR function.

Cryo-EM, crystallography, biochemical experiments and computational approaches have been used to study different intermediate states of the Aeromonas hydrophila toxin aerolysin en route to pore formation. These results reveal that an unexpected and marked rotation of the core aerolysin machinery is required to unleash the membrane-spanning regions.

DNA in the cytosol activates immune responses by binding sensors such as cGAMP synthase (cGAS). A set of studies reveal the structural mechanism of DNA sensing and show that cGAS produces a cyclic 2′-5′-linked dinucleotide, a new cellular second messenger.

Analysis of the yeast ATP-binding cassette transporter interactome provides insight relevant to human health on the regulation and function of a protein family that determines tolerance to physiological conditions and externally imposed stress.

In vivo, hydrogenases require maturases for active site incorporation. However, in vitro, an active site model with limited catalytic activity could be incorporated into the apo form of [FeFe]-hydrogenase without the aid of maturases, generating enzyme with native activity.

Biological sulfonate incorporation is mediated by 3′-phosphoadenosine-5′-phosphosulfate–dependent sulfotransferases and, to a lesser extent, arylsulfate sulfotransferases. An unusual two-enzyme strategy for sulfonate mobilization involving both types of sulfotransferases has been revealed during antibiotic biosynthesis, which uses a new polyketide as the sulfonate shuttle.

Vitamin B₁₂–dependent radical enzymes that can undergo irreversible inactivation during catalysis have their own chaperones for the maintenance of catalytic activities. New research defines a mobile loop in the G protein that determines chaperone function and defines a switch III motif akin to that found in classical G proteins.