Volume 15 Issue 1, January 2019

Prostanoids signal through G-protein-coupled receptors to regulate diverse physiological processes. Structures of three prostanoid receptors in inactive and active conformations now uncover the molecular determinants of ligand recognition and receptor activation and offer new opportunities for drug discovery.

Phase separation underlies the formation of cellular membrane-less organelles. A new report identifies deacetylation at lysine residues of intrinsically disordered protein regions to drive liquid droplet formation in vitro and stress granule maturation inside cells.

Characterization of a novel mutation in the E2 ubiquitin-conjugating enzyme UBE2A accounts for the decreased activity of the mutant enzyme that underlies disease and provides important insight into the catalytic mechanism of E2s.

Structural analysis of prostaglandin E receptor EP3, a member of the prostanoid receptor subfamily of GPCRs, in complex with the endogenous agonist PGE₂ reveals important interactions and motions required for receptor activation.

A structure of the prostaglandin E₂ receptor 3 (EP3) bound to the agonist misoprostol shows a completely enclosed binding pocket with a structured water molecule that coordinates misoprostol's ring structure and explains the receptor's selectivity.

The structure of human prostaglandin E receptor EP4 in complex with antagonist ONO-AE3-208 and a functional antibody reveals a ligand-binding site at the interface of the lipid bilayer that is unique among GPCRs.

Structures of the human thromboxane A₂ receptor, a member of the prostanoid family of G-protein-coupled receptors, in complex with two synthetic antagonists reveal that ligands access the ligand-binding pocket from the plane of the lipid bilayer.

Co-opting the amyloid machinery from Bacillus subtilis, engineering of TasA fusion proteins enables the assembly of functionalized biofilms with tunable physicochemical properties that are amenable to 3D printing and microencapsulation techniques.

HIP1R directly interacts with PD-L1 and targets PD-L1 for lysosomal degradation. Development of a rationally designed peptide incorporating the PD-L1 binding sequence of HIP1R with a lysosomal targeting sequence promotes PD-L1 degradation.

HDAC6 modulates acetylation at multiple lysine residues in the N-terminal intrinsically disordered region of RNA helicase DDX3X to regulate liquid–liquid phase separation and stress granule maturation.

Structural and biochemical analysis of a UBE2A mutation linked to intellectual disability reveals that the Q93E mutant perturbs the E2 catalytic microenvironment essential for lysine deprotonation during the ubiquitin-transfer process.

A class of nepetalactol-related short-chain dehydrogenase/reductases (NEPS) captures a reactive enol intermediate produced by iridoid synthase for cyclization and subsequent oxidation into nepetalactones, the active ingredients in catnip.

The observation that transcription activator-like effectors (TALES) displace TALES bound at adjacent downstream DNA enables engineered regulation of gene expression, displacement of other DNA binding proteins and construction of logic-gated systems.

ZCCHC4 was identified as a mammalian ribosome RNA (rRNA) N⁶-methyladenosine (m⁶A) writer protein that installs m⁶A 4220 in 28S rRNA. 28S rRNA methylation affects global translation and cell growth and contributes to tumorigenesis in cancer cells.