Volume 16 Issue 12, December 2020

The ADGRL3 receptor, a member of the adhesion G-protein-coupled receptor family, is implicated in many neurological diseases. Using a novel technique involving controlled proteolysis of the receptor’s extracellular domain, this study demonstrated that ADGRL3 signals via G12/13 G proteins.

Altered glycosylation helps cancer cells evade immune destruction, and targeted remodeling of glycans in vivo offers the ability to reprogram immune responses. A stable chemical linkage between an antibody and neuraminidase enables the targeted destruction of self-associated sialic acids to enhance antitumor immunity.

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 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 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.

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 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 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.

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.

Among the adhesion receptor class of GPCRs, which are understudied, the adhesion receptor ADGRL3 can be activated by its own tethered agonist and couples to G protein G12/13 and somewhat to Gq.

Genetic screens reveal a compendium of metabolic modifiers of lipid peroxidation. Tetrahydrobiopterin is essential under GPX4 inhibition, acting as a radical-trapping antioxidant that inhibits lipid peroxidation and is regenerated by DHFR.

Imaging of phosphatidylcholine, sphingomyelin and their interorganelle lipid transport in live cells, using azido-choline and a spatially limited bioorthogonal tag, suggests that autophagosomal membranes originate from the ER.

Cryo-EM structural work shows sterols binding at four adjacent locations within the class F GPCR Smoothened (SMO), where the transmembrane core functions as a sterol tunnel in which occupancy activates SMO for downstream Hedgehog signaling.

An αHER2 antibody–neuraminidase conjugate, which selectively targets the removal of sialic acids from glycans on breast cancer cells, bypasses a glycoimmune checkpoint and enhances tumor cell killing by the host immune system.

A mitochondria-activatable bioluminescent probe was designed enabling sensitive, non-invasive and longitudinal monitoring of mitochondrial membrane potential in vitro and in vivo.

NADP can directly bind with FTO and enhance its m⁶A demethylase activity, thus affecting RNA m⁶A modification and adipogenesis.

An irreversible small-molecule inhibitor of histone methyltransferase NSD1 is developed, which binds covalently to the C2062 residue in the catalytic SET domain and represses H3K36 dimethylation and target gene expression in leukemia cells.

The combination of heavy isotope labeling and ultra-high-pressure liquid chromatography coupled to triple-quadrupole mass spectrometry (UHPLC–MS) is used to quantify modified genomic cytosines in pluripotent stem cells in different states and reveals active turnover of methylcytidine in oxidation-dependent and oxidation-independent manners.

The whitefly Bemisia tabaci defends against plant glucosinolate toxins by serial addition of glucose moieties catalyzed by a pair of glycoside hydrolases, preventing toxin activation during feeding on the plant tissue.

A cell-free system for cannabinoid production uses only low-cost inputs with 12 enzymes and can operate either aerobically or anaerobically, in addition to reducing ATP requirements by use of an engineered system for malonate-CoA biosynthesis.

Incorporation of the non-canonical amino acid 3-aminotyrosine into the chromophores of green fluorescent protein-based biosensors systematically red-shifts their fluorescent properties while maintaining brightness, dynamic range and responsiveness.