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Producing artificial spider silk with the same tensile strength and elasticity as native silk has historically been difficult. The cover shows new, stronger artificial spider silk produced using an extremely soluble chimeric spider silk protein and a biomimetic spinning method that mimics the narrow duct and acidity changes met by the natural silk protein in the spider glands. Cover design by Erin Dewalt, based on an image created by Lena Holm. Brief Communication, p262
Differential redox regulation of kinase isoforms serves to provide intricate control of cellular signaling events. In a new study, a single isoform of Akt, Akt3, is shown to be preferentially modified by lipid-derived electrophiles to modulate downstream signaling events in mammalian cells and zebrafish.
Bioengineers have endowed a consortium of human cells with an artificial sense of smell, enabling the cells to detect, quantify, and remember the presence of gaseous volatile compounds in their environment.
A new mechanism of functional crosstalk between two distinct G-protein-coupled receptors (GPCRs)—the parathyroid hormone receptor (PTHR) and β2-adrenergic receptor (β2 Ar)—that occurs at the level of G protein βγ subunits and a specific adenylyl cyclase isoform is identified. This crosstalk augments cAMP signaling by the PTHR from endosomes, and thus promotes the actions of PTH ligands in bone target cells.
Recent advances in metabolic engineering provide possible new approaches for the production of advanced intermediates as tractable semisynthetic starting materials for alkaloid-derived pharmaceuticals and potential new drugs.
The synergistic effect of the GPCR β2AR on signaling through another GPCR, PTHR, is explained by the release of Gβγ from the heterotrimeric Gαiβγ protein, activating adenylate cyclase AC2 and subsequent prolonged cAMP signaling in internal compartments
The combination of an extremely soluble chimeric spider silk protein (spidroin) and a biomimetic spinning method that recapitulates the endogenous pH gradient in silk glands produces a remarkably strong artificial spider silk.
A structural study of MraY, an essential enzyme from Clostridium bolteae involved in bacterial cell wall synthesis, in complex with the natural product antibiotic tunicamycin, provides a basis for future antibiotic design.
Orthogonal cholesterol sensors that are useful for imaging cholesterol in the plasma membrane leaflets reveal an asymmetry in which a high outer leaflet concentration is important for signaling processes and is potentially actively maintained.
Structural characterization of the bifunctional enzyme linalool dehydratase isomerase and exploration of its substrate scope demonstrate its potential for catalyzing desirable transformations of various tertiary alcohols.
SHAPE and DMS in vitro chemical probing analysis reveals the secondary structure of the RepA long noncoding RNA, and UV-cross-linking and RNA modeling analyses produce a 3D model of RepA depicting phylogenetically conserved domains.
Crystallographic snapshots illustrate the catalytic cycle and illuminate the mechanism by which the enzyme Pdx1 shuttles intermediates between lysine residues in its two active sites during the biosynthesis of pyridoxal 5′-phosphate.
In vitro selection of RNA libraries constructed by randomization of RNA structural scaffolds from known ribozymes and riboswitches led to the identification of aptamers that were readily translated into functional biosensors in cells.
The use of an alkyne–adenosine analog enables the labeling and detection of ADP-ribosylated proteins under oxidative stress and reveals a role of Hras ADP-ribosylation to regulate its signaling.
A synthetic biology approach involving engineered mammalian cell consortia converts analog sensing of fragrance molecules into control of reporter-gene expression and amplifies the signal, thus enabling the digitization of molecular signals for cybernetic devices.
SUV4-20 members mediate the di- and trimethylation of lysine 20 on histone H4. A chemical screen led to the identification of A-196 as a potent and selective inhibitor of SUV4-20 that decreases H4K20 methylation and alters DNA damage response.
Discovery and characterization of two Brønsted acid enzymes from quinolone alkaloid biosynthesis provides new biocatalytic approaches for the challenging but synthetically useful cationic rearrangement of epoxides.
The use of the T-REX redox targeting platform to identify proteins that react with lipid-derived electrophiles in cells and zebrafish reveals that hydroxynoneal (HNE)-mediated modification of Akt3 C119 decreases Akt3 activity.