Volume 11 Issue 3, March 2015

Aggregation of α-synuclein (αSN) is critical to the development of Parkinson's disease (PD), but the role of membranes in this process has been unclear and controversial. Galvagnion et al. demonstrate and model how lipids can stimulate αSN aggregation over a narrow range of lipid:protein stoichiometries.

Microbial natural products and the specific subset with antibiotic activity, 'the antibiotic'ome', consist of a dizzying array of structures and exert their effects by many known modes of action. In this issue, Cociancich et al. describe a unique natural product that—along with a compound identified in a recent publication by Baumann et al.—defines a new antibacterial chemical scaffold that acts on a rarely hit target, DNA gyrase subunit A.

Although resveratrol is thought to provide many beneficial health effects, its cellular targets and mechanism of function are still under investigation. A new study found that resveratrol binds to tyrosyl transfer-RNA synthetase, resulting in the activation of the stress response effector PARP1.

The physical arrangement of enzymes within native metabolic pathways is emerging as an important but underexplored area of molecular biology. Recent advances in mass spectrometry enabled confirmation of the proposal that the Krebs cycle enzymes form a complex and suggest that substrate channeling is the most likely benefit to this structural arrangement.

This Perspective describes the different modes by which bacteria belonging to a population can achieve resistance to antibiotic treatments that are otherwise lethal to individual cells and suggests that such mechanisms of collective antibiotic tolerance can be targeted for development of antimicrobials.

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.

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.

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.

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.

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.

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.

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.

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.