Editors' Choice

Science  09 Nov 2007:
Vol. 318, Issue 5852, pp. 888

    Three Times Two Is Six

    1. Gilbert J. Chin

    Photosynthetic organisms take advantage of an abundance of nitrogen by storing it as arginine (whose side chain contains a nitrogen-rich guanidinium group), a reaction that is catalyzed by the dimeric protein N-acetylglutamate kinase (NAGK)—an enzyme that is, not surprisingly, subject to feedback inhibition by arginine. PII proteins are one of the central metabolic coordinators of carbon and nitrogen fluxes; this protein is a homotrimer and has been shown previously to regulate ammonia influx into cells by inserting its T loop into the cytoplasmic vestibule of the trimeric ammonia channel; too much of a good thing can be hazardous to one's acid/base equilibrium.

    Llácer et al. describe structural and biochemical studies of the interaction between PII and NAGK in the cyanobacterium Synechococcus. They show that a hexameric ring (a trimer of dimers) of NAGK is sandwiched by a pair of PII trimers, so that each of the six PII subunits makes a reversible contact covering about 600 Å2 with a single NAGK subunit. Each NAGK dimer is oriented at an angle to the plane of the ring, as in the blades of a propeller, and the binding of PII increases the angle slightly. The arginine-binding sites are located at the interdimer surfaces, and tilting the dimers and altering the interdimer contacts reduces the binding affinity for arginine by 15-fold. Unlike its direct inhibition of the ammonia channel, the effect of PII binding on NAGK, though also mediated in large part by the T loop, is entirely indirect and distant from both the catalytic and allosteric sites.— GJC

    Proc. Natl. Acad. Sci. U.S.A. 104, 17644 (2007).


    Death by Consumption

    1. Stephen J. Simpson

    Regulatory T (Treg) cells continue to command attention in the minds of immunologists, not least because the mechanisms by which they exert their suppressive effects remain obscure. Although one possibility is that Treg cells paralyze particular functions in effector T cells, Pandiyan et al. present evidence that they can starve their targets to death. When the two types of T cells were placed in culture together, the effector (also called the responder) CD4+ T cell population eventually underwent cell death in a manner reminiscent of that seen when T cells are deprived of cytokines. It emerged that the Treg cells were consuming the growth factor interleukin 2 (IL-2), and possibly other cytokines as well. This depletion appeared to operate only when the two types of cells were in close proximity, suggesting that the balance between the supply of secreted cytokines and the voraciousness of the Treg cells might be an important factor. Cell death by cytokine withdrawal was controlled by intracellular mediators, such as the pro-apoptotic protein Bim, and Bim-deficient responder T cells were able to resist suppression by Treg cells. Cytokine consumption by Treg cells was also found to block pathogenic T cells in a mouse colitis model, suggesting that this mechanism might be broadly involved in regulating pro-inflammatory T cells. — SJS

    Nat. Immunol. 8, 1353 (2007).


    From Pathogen to Polymer?

    1. Jake S. Yeston

    Diagnosing diseases would ideally entail simple, rapid, inexpensive tests with both high sensitivity and high specificity. One widely applied approach at the molecular level has been the enzyme-linked immunosorbent assay (ELISA), in which an antigen associated with the disease is induced to bind with an antibody attached to an enzyme. A substrate is then added that the enzyme can modify to elicit a visible response, such as fluorescence, for quantification. In some cases, however, ELISAs can be complicated to implement and may not offer the requisite sensitivity. Sikes et al. present a promising preliminary exploration of an alternative approach, in which the enzyme is replaced by a synthetic photoinitiator of free-radical polymerization. Specifically, the authors appended ∼140 initiators and one or two avidin derivatives to each chain in a sample of acrylic acid/acrylamide copolymer. They then exposed a surface functionalized with biotin to this sensing polymer and detected avidin-biotin binding by adding aqueous acrylate monomers and irradiating the samples with ultraviolet light to induce polymerization where the initiators were bound. A 10-min irradiation time was sufficient to produce visible white polymer spots on samples containing as few as 1000 biotin sites: a response several orders of magnitude more sensitive than an enzyme-based assay applied to the same system. — JSY

    Nat. Mater. 10.1038/nmat2042 (2007).


    From Fat to Fusion

    1. Stella M. Hurtley

    In diabetes, lipid droplets can often be seen to accumulate in muscle and liver cells. The extent to which individual lipid droplets interact within the cell is not very well understood. Boström et al. describe how such intracellular lipid droplets can grow within a cell by the fusion of individual droplets; this merging is promoted by components of the intracellular vesicle fusion machinery, which are better known as the molecular mediators of transport vesicle fusion with their target membranes. Lipid droplets from fibroblast cells in culture were isolated by cell fractionation and shown to contain several proteins, including members of the so-called SNARE family of membrane fusion proteins. In an assay of lipid droplet fusion in living cells, the knockdown of lipid-droplet-associated SNAREs reduced the number of fusion events observed by up to 75%. Furthermore, in muscle cells, the co-opting of one of the SNAREs, SNAP23, to lipid droplets (for example, by adding increasing amounts of the fatty acid oleic acid) may play a role in the development of insulin resistance by diverting the SNARE from its normal function in delivering glucose transporters to the cell surface in response to insulin. — SMH

    Nat. Cell Biol. 9, 1286 (2007).


    Atom Gyroscopes

    1. Ian S. Osborne

    We terrestrials tend to get our bearings from compass readings, tracking the stars, or more recently in a digital format from global positioning systems. For the likes of satellites, orbiting telescopes, and probes navigating through deep space, the systems of choice to point the way are based on gyroscopes aligned with a distant reference star. To study predictions of general relativity such as frame dragging, the effects of which would be seen as tugs on the rotation axis of the gyros, high sensitivity of the gyroscopes to rotation is a prerequisite. In this context, atom interferometers can surpass mechanical gyroscopes or optical interferometers by orders of magnitude. Wu et al. report on the development of a cold-atom interferometer in which a matter wave of Rb atoms is split in two, with both halves sent around opposite paths repeatedly and brought together again to produce an interference pattern. The phase shift is sensitive to the rotation of the interferometer. — ISO

    Phys. Rev. Lett. 99, 173201 (2007).


    Picking Partners

    1. Jake S. Yeston

    The evolution of strategies for synthesizing complex organic molecules relied in large part on a deepening understanding of the relative reaction rates of often subtly differing functional groups. Rational assembly of larger, supramolecular structures, which are held together by an array of noncovalent interactions, is now proceeding along a similar course, with predictive principles emerging from careful systematic studies. In this vein, Aakeröy et al. have explored the competition between hydrogen and halogen bonding in the cocrystallization of several small aromatic building blocks. One crystallizing partner contained two nitrogen sites (pyridine and benzimidazole), each of which could potentially act as an acceptor toward either a polarized hydrogen or a halogen. The donor partners each bore an oxime (CH=NOH) group, which could interact through either the C-H or the O-H site, as well as a fluorine, bromine, or iodine substituent poised for halogen bonding. Crystallography revealed that in all three cocrystals, the benzimidazole N formed an H bond with the oxime OH. In the F- and Br-substituted systems, the pyridine N attracted the C-H group; only in the iodo case did a halogen bond form instead. — JSY

    J. Am. Chem. Soc. 129, 10.1021/ja073201c (2007).


    Stages of Growth

    1. Marc S. Lavine

    Many important catalysts are composed of supported metal nanoparticles. Although x-ray absorption spectroscopy has been used to probe the impact of particle size and shape on chemical reactivity, it is difficult to extract information beyond the first few coordination shells, and there is a risk with this technique of radiation damage to the samples. Chupas et al. show that by monitoring the change in pair distribution functions from the scattering of weakly absorbed (and thus minimally damaging) high-energy x-rays, they can track the growth of Pt0 nanoparticles with time. They studied the reduction of PtCl62−, supported on titanium dioxide, at temperatures from 100° to 200°C. The Pt-Cl correlations decreased linearly with time without an induction period, suggesting that the reduction is not autocatalytic, as has been seen for Pt4+ species in solution. Data collected during the heating period revealed a shift in the dominant process from reduction of the Pt ions (to make isolated metal atoms or small clusters), to rapid growth or sintering, and finally ripening of the larger clusters. — MSL

    J. Am. Chem. Soc. 129, 10.1021/ja076437p (2007).