Reviews & Analysis

Single-step site-specific labeling of native proteins is one of the holy grails in the chemical biology field. 2-Pyridinecarboxyaldehyde derivatives are shown to react selectively at the N terminus of proteins to form stable conjugates, irrespective of the nature of the N-terminal amino acid, enabling the straightforward introduction of useful functional groups into a wide array of proteins.

Heterodimerization of G protein–coupled receptors can lead to the activation of intracellular pathways that are not triggered by either of the individual receptors. This property may lead to the development of new therapeutic approaches showcasing increased efficiency and selectivity.

The demonstration of excitation energy dissipation via energy transfer in a cyanobacterial chlorophyll-carotenoid membrane complex provides evidence that this mechanism may also operate in the light-harvesting complex antennae of higher plants.

Bacterial translation elongation factor P (EF-P) is essential to overcome ribosome stalling at polyproline stretches during protein synthesis. A new mechanism of EF-P activation, identified in a subset of Bacteria, involves addition of the sugar L-rhamnose to a critical arginine residue.

This Perspective discusses recent advances in understanding the structural and pharmacological properties of the downstream Hedgehog pathway effector Smoothened. Small molecule agonists and antagonists of Smo could be used as potential therapeutics.

Cytosolic proteins can be modified cotranslationally by the installation of O-GlcNAc groups onto serine and threonine residues. This modification suppresses cotranslational ubiquitination and stabilizes proteins against proteasomal degradation.

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.

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.

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.

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.

The reliable identification of microRNA (miRNA) targets remains an elusive goal. A new technique, using specially modified synthetic miRNAs to directly capture bound RNAs, brings us closer.

Lysophosphatidylserines (lyso-PSs) are an emerging class of signaling lipids implicated in human inflammatory and autoimmune diseases. A newly discovered phosphatidylserine-specific lipase, ABHD16A, together with the recently described lyso-PS lipase ABHD12 shed light on the in vivo regulation of lyso-PS, providing a potential enzymatic target for modulating neuroinflammatory responses.

An international group of chemical biologists convened in San Francisco to present the latest scientific findings, discuss future directions and be inspired by research at the interface of chemistry and biology. This report on the third annual conference of the International Chemical Biology Society provides a brief overview of the meeting and its scientific program.

Recent studies on two enzyme classes operating at the membrane interface showcase an unanticipated degree of structural plasticity involving domain swapping and marked secondary structure reshuffling. This structural variability in topology is key to functional diversification and catalytic prowess.