Research articles

The lack of existing tools has made it difficult to detect and quantify methionine sulfoxide in cells. The introduction of the MetSOx and MetROx fluorescent sensors allows detection of stereospecific forms of methionine sulfoxide in cells.

O-GlcNAcylation is a known post-translational modification, but analysis of nascent proteins now demonstrates that it also occurs during translation, preventing proteolytic degradation of modified proteins by blocking ubiquitination.

Several GPCRs have ligands that act as pharmacological chaperones that rescue function of mutated receptors. This formed the basis of a screening strategy to identify new ligands for Frizzled4 that act allosterically at an effector domain to inhibit β-catenin signaling.

Establishing the existence of a Diels-Alderase—an enzyme that catalyzes a concerted [4 + 2] cycloaddition—is made easier by a crystal structure of SpnF, which, along with computational and biochemical analysis, should enable mechanistic investigations.

The discovery of two new types of enzymes that act in tandem within the spirotetramate biosynthetic pathway to catalyze [4+2] cycloadditions offers new opportunities for mechanistic investigations of potential Diels-Alderases.

Technologies that bias GPCR expression for formation of heterodimers show that, when heterodimerized, α_2C-AR and AT-1R exhibit atypical G_s-cAMP-PKA signaling upon ligand stimulation compared to either parent receptor expressed alone and mimic activation associated with arterial hypertension.

Light-harvesting complexes (LHCs) manage energy flux into photosynthesis and dissipate excess light energy. The demonstration of dissipative energy transfer from chlorophyll-a to β-carotene in cyanobacterial high light–inducible proteins provides a mechanistic model for similar processes in LHCs.

A screen for compounds that inhibit disulfide bond formation in β-galactosidase in Escherichia coli found inhibitors of the membrane enzyme DsbB. Given the importance of DsbB in bacterial virulence, the inhibitors are potentially useful as antibacterials.

N-linked glycosylation of a conserved arginine in the translation elongation factor EF-P by a newly discovered rhamnosyltransferase EarP is needed to rescue ribosomal stalling at polyproline-encoding sequences in β-proteobacteria and other species.

Modification of the CRISPR/Cas9 genome editing system by the addition of the light inducible proteins CRY2 and CIBI1 enables blue light–mediated transcription of endogenous genes in mammalian cells.

A series of designed peptides call the sphere of influence of the helix macrodipole into question, showing that the favorable rotamers allowed by K→E hydrogen bonds beat out the entropically penalized but macrodipole-aligned E→K hydrogen bonds.

Small unilamellar vesicles composed of the negatively charged lipid DMPS enhance the aggregation of the Lewy Body disease protein α-synuclein by increasing the rate of primary nucleation by a thousandfold.

RNA has been used in a variety of synthetic biology circuits but never as a transcriptional activator. Two design strategies using synthetic and natural sequences now lead to RNA activators, enabling RNA-only logic gates.

Reversible transcriptional repressors are built with TALE proteins on the basis of steric hindrance of a new promoter architecture in an RNA-sensitive manner, enabling applications in mammalian cells such as classification of cancerous versus noncancerous cells.

Membrane sorting of Ras and its isolated lipid anchor is based on membrane curvature, sensed by Ras itself. This helps to explain the previous inability to match in vivo results in vitro in promoting the raftophilic Ras to partition with membrane lipid rafts.

Inhibitors of the PAD4 enzyme that bind the inactive enzyme link this protein deiminase and the resultant arginine-to-citrulline modification to formation of neutrophil extracellular traps, highly decondensed chromatin structures with both host-defense and pathological roles.

The natural product albicidin is known to be a potential antibacterial agent, but its missing structure has stymied further studies. Structural determination and biochemical tests of NRPS domains now identify an unusual p-aminobenzoic acid–based compound.

The construction of ClpX hexamers containing variable numbers and configurations of wild-type and grip-defective pore loops supports a model of concurrent loop movement that ensures substrate unfolding and translocation.

ABHD16A is identified as a major enzyme catalyzing production of lyso-PS from phosphatidylserine (PS). A new ABHD16A inhibitor and knockout mice show a dynamic interplay occurring during inflammation between ABHD16A and disease-linked ABHD12, an enzyme that degrades lyso-PS.

The metabolic enzyme GAPDH exhibits oxidative inactivation in response to H₂O₂. A proton relay system was identified that enhances H₂O₂ sensitivity of GAPDH distinct from its catalytic activity, which ensures viability under oxidative stress.