News & Views in 2009

The RNA-activated protein kinase PKR inhibits translation initiation by sensing long viral double-stranded RNA. A new report indicates that PKR is also activated by a cellular mRNA, but only when ribosomes are not initiating translation.

Two iron regulatory proteins (IRP1 and IRP2) regulate translation and/or stability of mRNAs encoding proteins required for iron storage, acquisition and utilization. Rather than IRP2 directly sensing iron concentrations, iron has been shown to regulate the level of the SKP1-CUL1-FBXL5 E3 ubiquitin ligase protein complex, which is responsible for IRP2 degradation.

Vibrio cholerae produces cholera autoinducer-1 (CAI-1), a signaling molecule previously believed to be synthesized by the CqsA enzyme. Here it is shown that CqsA does not directly synthesize CAI-1; instead, it synthesizes amino-CAI-1, which is then converted into CAI-1 in a CqsA-independent manner.

A unique heterotrimeric assembly of individually inactive paralogs, two of which are also involved in regulating phosphatase activity, creates one of the key enzymes of coenzyme A biosynthesis in yeast, pointing to the possibility of a previously undescribed cross-talk between metabolic and signaling pathways.

Synthetic biologists aim to rationally design and construct useful biological circuits. However, perturbation of host cell physiology, through the very process of turning on an artificial circuit, can give rise to unexpected emergent behaviors, such as bistability.

Few antimicrobial drugs function by directly targeting RNA. A small molecule that binds the hepatitis C viral genome by 'locking' in a particular RNA conformation to inhibit viral protein production suggests a new paradigm for drug design.

Membrane curvature sensing by amphipathic helices is an emergent property of the ensemble of molecules and membrane sites. New data suggest that individual molecules do not experience stronger binding to curved membranes.

Parathyroid hormone (PTH) and PTH-related protein activate the same receptor but can produce divergent effects. Reports now describe two active conformations for the PTH receptor, one of which moves intracellularly—complexed with hormone and G protein—to produce a continued cAMP signal.

Hydrolysis of the phosphodiester linkages in DNA is a notoriously difficult reaction. Deoxyribozymes that use Zn²⁺ and Mn²⁺ ions to accelerate this reaction by a factor of one hundred million (or more) have been identified and characterized.

Chemo-metabolic processes such as redox remodeling and amino acid availability act as immunity rheostats, revealing a new mechanism regulating intercellular cross-talk between dendritic cells, regulatory T lymphocytes and effector T lymphocytes.

The functional architecture of dimeric or oligomeric GPCR signaling remains incompletely understood. Using a clever combination of receptor–G protein fusions and various receptor mutations, new research provides a glimpse into how oligomers might be arranged with respect to the G proteins they interact with.

One of the primary functions of the Golgi apparatus is the assembly of glycans on macromolecules destined for secretion or the plasma membrane. A recent study describes the first step toward an artificial Golgi, based on a microfluidic chip and magnetic nanoparticles.

A small-molecule inhibitor of the obligate dimeric protease of human Kaposi's sarcoma–associated herpesvirus was identified. The agent functions by a 'monomer trap' mechanism in which the compound binds to a partially unfolded monomer and disrupts the formation of the enzymatically active protease dimer.

A cocrystal structure of the enzyme that synthesizes selenocysteine reveals the elegantly simple recognition mechanism for the tRNA molecule for this '21^st amino acid'. The structure resolves some mechanistic questions and allows for comparison of the tRNA-dependent synthesis of cysteine and selenocysteine.

Screening a library of expressed cyclic peptides identified clones that reverse the cytotoxicity of α-synuclein in yeast and Caenorhabditis elegans. The results suggest a new approach for intervention in Parkinson's disease, and perhaps a druggable target.

The parallel determination of more than 100 absolute intracellular metabolite concentrations by isotope-labeled HPLC-MS allowed a comprehensive analysis of the cellular state, its metabolic capacities and modes of regulation. Among other findings, it became obvious that for most enzymes the concentrations were above the K_m values, which indicates a trend toward saturation of most enzyme active sites.