Volume 16 Issue 10, October 2020

A new molecule that specifically activates a key protein homeostasis pathway has been identified. The ability to initiate the IRE1–XBP1s branch of the unfolded protein response opens up new avenues for basic research and treatment of disease.

Coherent Raman imaging enables mapping of chemical features at subcellular resolution, setting the stage for tracking lipids and other metabolites in intact living systems.

The electrogenic bacterium Geobacter synthesizes conductive extracellular nanowires to facilitate electron transfer that powers respiration. A highly conductive form of these nanowires is now revealed to be composed of oligomers of an 8-heme cytochrome, OmcZ.

Virulence factors from various bacterial pathogens catalyze post-translational modification of key host proteins, including phosphate β-elimination and phosphoribosyl-linked ubiquitination, to suppress host immune defenses and promote infection.

Highly selective activators of IRE1/XBP1 splicing pathway were identified via high-throughput screen, which promoted the degradation of APP and reduced APP-associated mitochondrial toxicity in an IRE1-dependent manner.

An orthogonal O-glycan biosynthesis system was engineered in Escherichia coli to support the production of glycoproteins displaying human mucin O-glycans, including Tn antigens, in living bacteria and in cell-free extracts.

Structural and biochemical analysis reveal that tetracenomycin X acts as an inhibitor of protein synthesis by binding within the exit tunnel in a large ribosomal unit to prevent the prolongation of the nascent polypeptide chain.

TAp63α monitors the genome integrity in oocytes. After DNA damage, TAp63α is activated, involving multiple phosphorylation steps by CK1 with different kinetics due to an unusual CK1/TAp63α interaction in which the product of one step inhibits the next.

A Raman-based imaging approach that can distinguish closely related chemical species used to characterize the distribution of lipids throughout the body of intact Caenorhabditis elegans worms shows that the epidermis is an important fat-storage reservoir.

Characterization of the interaction between PTH and its G-protein-coupled receptor, PTHR, shows conformational changes coupled to residues interacting with His9, which helps position the PTH N terminus at the PTHR transmembrane domain to facilitate β-arrestin coupling.

A new ligand against the GPCR GLP-1R acts as a positive allosteric modulator, binding both the receptor and the orthosteric ligand, accessing the peptide ligand within the interface between transmembrane domains 1 and 2 of the receptor.

A robust mass spectrometry workflow was developed for rapid drug perturbation profiling in multiple cell lines, enabling improved mechanistic deconvolution of single compounds and revealing novel mechanisms of action.

TH1760 is a first-in-class, potent, selective and cell-active inhibitor against human NUDT15, which sensitizes cells to 6-thioguanine treatment. TH1760 represents a valuable tool for deciphering the enigmatic functions of NUDT15.

A method combining multiplexed genome engineering, genetic code expansion and biorthogonal chemical labeling has been developed for multiple site-specific protein labeling and used to label ribosome components at sites hard to access for FRET assays.

Application of an electrical field to Geobacter sulfurreducens biofilms stimulates production of OmcZ nanowires, which undergo a pH-induced conformational switch that causes increased stiffness and conductivity due to enhanced heme group π-stacking.

Utilization of structural proteins with intrinsically disordered regions enables the formation of membraneless organelles in Escherichia coli through liquid–liquid phase separation, as well as their functionalization with active enzymes.