Reviews & Analysis

Lysophosphatidic acid, a lipid mediator, second messenger and intermediate in lipid biosynthesis, finds a new intracellular target in TRPV1. This nonselective cation channel is also targeted by the analgesic capsaicin, which acts to desensitize the channel.

The multisubunit DNA polymerases of eukaryotes have iron-sulfur centers that are crucial for polymerase assembly and therefore the integrity of the nuclear genome.

Amino acids not only are useful for protein synthesis but also act as regulators of gene expression. An elegant genome-wide approach now shows how binding of amino acids to transcription factors regulates an integrated network of amino acid metabolism to suit the physiological needs of bacterial cells.

Designed expansion of hydrophobic contacts converts a coiled-coil tetramer to a true hexamer, a new protein fold previously deemed unlikely to exist. The complex has a central channel sized to allow passage of water molecules.

Cell membrane–bound G protein–coupled receptors are traditionally thought to stimulate cell proliferation by addressing the nuclear replication machinery, but we now learn that they also activate cytosolic nucleotide factories, the purinosomes.

The monoclonal antibody 3B5H10 that recognizes diffuse mutant huntingtin predicts cell death in primary striatal neurons. Biochemical and biophysical analyses reveal that the 3B5H10 epitope is exposed in a monomeric state, identifying this specific conformation as a toxic agent in Huntington's disease.

Proteins binding to lipid moieties of GTPases can extract the GTPases from membranes. An innovative study shows that Arl2 and Arl3 act as dissociating factors that allosterically squeeze the lipid moiety of a GTPase from the grip of a lipid-binding protein, thereby facilitating reincorporation of the GTPase into membranes.

The large number of available chemical strategies to modify biomolecules can be overwhelming and time-consuming if adopted without careful consideration. Applying chemical logic to select context-dependent protocols can streamline this process substantially, leading to a wealth of functionalized materials for use in biology and materials science.

By seeking to replicate either specific biochemical reactions or the chemical logic employed by cellular machinery, biomimetic synthesis serves to both inform and test proposals for natural product biosynthesis as well as expand and redefine the rules of organic chemistry.

For years scientists have debated whether glycans, like DNA, RNA and proteins, have a true sequence. In a recent study, researchers show that the proteoglycan bikunin has a defined and predictable sequence, opening the door for a new understanding of the glycome.

The first selective inhibitor of monogalactosyldiacylglycerol (MGDG) synthase was identified from a chemical library screen. The competitive inhibitor effectively targets MGDG concentrations across plant tissues and was used to demonstrate a new role for galactolipids in pollen-tube development.

Crystal structure and drug pharmacophore structure-activity data guided a combined mutagenesis and chemical screen to develop ligand-gated ion channels activated by unique chemical agonists. Through genetic engineering, these channels can be used to manipulate neuronal excitability and dissect the neuronal circuitry responsible for complex behaviors.

The extent to which ligand-free GPCRs exist in quasi-stable 'precoupled' complexes with G proteins in vivo is uncertain. New research, using fluorescence recovery after photobleaching (FRAP), reveals a structural requirement for and functional consequences of muscarinic acetylcholine receptor–G_q protein preassembly.

Monitoring oxygen (O₂) levels is essential to optimizing aerobic metabolism and ensuring proper biological processes in most eukaryotes. The spice chemosensor TRPA1 is a previously unidentified O₂ sensor in the mammalian sensory nervous system that warns against hyperoxia and hypoxia.

A recent flurry of activity has defined the protein FLOWERING LOCUS T (FT) as a mobile signal or 'florigen' that induces flowering. A new study has shown that a 14-3-3 protein links FT to a transcription factor at the plant apex to initiate flowering.

The glycosyltransferase-catalyzed generation of sugar nucleotides is normally an unfavorable endothermic process. Simple reactive glycosides used in conjunction with mutant transferases enable such reactions to become favorable exothermic processes, providing practical access to a diverse range of non-natural sugar nucleotides.

Purine riboswitches have served as models for riboswitch structure, dynamics, evolution and engineering. New crystallographic models reveal the adaptability of a purine riboswitch evolved to bind 2′-deoxyguanosine and highlight challenges inherent to riboswitch engineering.