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Cytoplasmic polyadenylation activates quiescent transcripts for translation by selective poly(A)-tail extension. An approach involving a clickable adenosine derivative permits capture of newly polyadenylated transcripts, and next-generation sequencing reveals mRNA sequence motifs that are linked to polyadenylation.
Inteins catalyze protein splicing, excising themselves from the final polypeptide sequence. Biochemical and structural analysis of multiple inteins now demonstrates that these constructs can swap domains before splicing, leading to unexpected hybrid products.
EZH2 and EED are components of the Polycomb repressive complex 2 (PRC2), a ‘writer’ complex involved in histone methylation. A stapled peptide that disrupts the EZH2-EED interaction arrests growth in PRC2-dependent leukemia cells and offers an alternative mode for EZH2 inhibition.
Opsinamides are nonretinoid inhibitors that compete with 9-cis-retinal for binding to melanopsin Opn4 without affecting rod- and cone-mediated visual responses but affecting tolerance to light and light exacerbation of migraine.
The metallothionein-like, 23-amino-acid peptide NO-inducible nitrosothionein does not protect against heavy metal toxicity like its homologues, but instead helps relieve nitrosative stress by reaction of six cysteine residues to form SNO adducts, which are recycled back to thiols by thioredoxin.
In cells, di-iron hydrogenases require three maturases to facilitate proper assembly of metal clusters. Reconstitution experiments with synthetic cofactor mimics coupled with functional and spectroscopic characterization now show these helper proteins are not needed in vitro to form highly active H2-producing catalysts.
Near-atomistic models of the prepore and membrane-inserted pore conformations derived from a combination of crystallography, cryo-EM, single-particle analysis, molecular simulation and modeling reveal a swirling mechanism of membrane insertion and pore formation by aerolysin.
Two families of sulfotransferases are known, but the natural sulfate source for the PAPS-independent enzymes was not clear. Investigation of the caprazamycin pathway reveals a type III PKS generates a chemical reagent that is sulfated by a PAPS-dependent sulfotransferase to generate the unknown sulfate donor.
A small-molecule activator of Wnt/β-catenin signaling acts by binding a negative regulator of β-catenin, Axin, leading to a conformational change that promotes association of Axin with LRP6.
The VCP ATPase has been linked to cancer, but the lack of well-defined, selective inhibitors has limited further investigation. A million-molecule screen now identifies a covalent inhibitor as well as an allosteric inhibitor that may freeze the enzyme in an ADP-bound conformation.
Monitoring the half-life of mutant huntingtin protein reveals how specific neurons are more susceptible to its toxic effects and to Huntington's disease.
Heterotrimeric G proteins contain a switch III motif that regulates enzyme function. Structural and biochemical studies now identify a similar switch III loop in a nonheterotrimeric G-protein chaperone that explains the debilitating effects of mutations linked to methylmalonic aciduria.
Structural and thermodynamic characterization of the interaction between the intrinsically disordered HBV protein preS1 and the human adaptor protein γ2-EAR indicates that the viral protein imitates host cell interaction motifs to gain access to the cellular trafficking system.
LuxR receptor and LuxI synthase homologs coordinate quorum sensing in several bacterial species. Investigations of a LuxR family member that is missing a LuxI partner define a pheromone signaling circuit that coordinates cell clumping based on recognition of its newly discovered ligands, the photopyrones.
An inhibitor of oxysterol-induced Smoothened activation defines a 20-OHC binding site in the extracellular domain of this essential component of the Hedgehog signaling pathway.
Mapping the yeast ABC transporter interactome suggests functional significance of transporter-transporter interactions and also shows function of some transporters in zinc homeostasis.