Reviews & Analysis

Pharmacological and genetic modulators of voltage-gated Ca²⁺ channel (Ca_V) activity have been useful tools for understanding and modulating excitable cell function. A new method combines these approaches to provide pharmacological control of a genetically encoded suppressor of Ca_V activity.

Multimodular scaffold proteins are ideally suited for assembling the various proteins in signaling pathways into supramolecular complexes. A recent study demonstrates that, in addition to a passive scaffolding role, a PDZ domain in a photoreceptor scaffold protein actively regulates fruit fly visual signaling via light-dependent conformational cycling.

DNA is the newest member of the enzyme club. The first glimpse of DNAzyme conformational changes at the single-molecule level reveals that enzymes made of DNA can use the same modi operandi as protein and RNA catalysts.

Nitric oxide–mediated production of cyclic guanosine 3′,5′-monophosphate (cGMP) is a crucial signal transduction pathway that controls a wide array of biological functions. A new layer of complexity in mammalian cell regulation is revealed by the discovery of a redox-active nitrated cGMP derivative with the ability to post-translationally modify protein thiol residues by S-guanylation.

A phosphorothioate modification of DNA has been identified in bacteria. This first observed alteration of the DNA phosphate backbone opens many questions about the mechanism of sulfur incorporation and the function of this modification.

A recently characterized 'M-box' genetic switch from bacteria is proposed to directly sense cellular Mg²⁺ levels through the conformation of its newly synthesized RNA. This Mg²⁺-sensing riboswitch controls transcription termination in front of a Mg²⁺ transporter gene, thus introducing a new and direct level of genetic regulation to metal ion homeostasis.

The C₁₂ 'earthy' odorant geosmin is derived from the C₁₅ metabolite farnesyl diphosphate. Metabolic transformation now seems to be catalyzed by a bifunctional protein having two operatively independent sesquiterpene synthase domains. The domains are catalytically linked through the passive diffusion of a C₁₅ alcohol product of the N-terminal catalytic domain to the C-terminal catalytic domain for the final steps of geosmin formation.

An emerging view is that high-fidelity metal selection by the proteins involved in metal homeostasis is pivotal to ensure that the correct metals bind to nascent metalloproteins. A new study demonstrates that the AztA zinc exporter performs this function by using tandem metal-binding domains to entrap some of the wrong metals in nonproductive complexes.

A fully synthetic three-component vaccine has been shown to induce high titers of antibodies against the mucin Tn antigen of human cancer cells. The vaccine's superior properties are a result of the covalent incorporation of a ligand for Toll-like receptors and the presentation of the vaccine in a liposome format.

Monitoring nutritional sufficiency is essential in optimizing bacterial survival strategies. Recent studies find that nutrient sensing is delocalized over many cell components. Adding to the complexity, some metabolite pools and cellular components contribute to more than one signal transduction pathway and to housekeeping functions.

Transmembrane electrochemical ion gradients are the thermodynamic forces exploited by living cells to drive specific substances across the membrane. A new study begins to reveal the molecular mechanisms by which a transporter protein harnesses these driving forces.

The use of biocatalysts for glycoside bond formation is an attractive strategy in chemical synthesis, but the tight specificity of enzymes can be a significant limitation. An ingenious screening strategy has led to the discovery of a particularly plastic glycosyltransferase.