Editors' Choice

Science  04 May 2007:
Vol. 316, Issue 5825, pp. 662

    Survival Aids

    1. Pam Hines

    Agarics—fungi that include the common mushroom—are diverse in morphology and in ecological niche: puffballs, gilled mushrooms, decomposers of wood, and mutualistic partners to ants. Alas, tracing their evolutionary radiations has been hampered by the dearth of fossil samples.

    Garnica et al. have performed a molecular analysis of nuclear genes and a microscopic analysis of agaric spore structures in order to better understand the organization of this group. Using these two features, they rearranged relationships, such that some species were flung apart and others recognized as more closely related than previously thought. It appears that one major evolutionary innovation led to the acquisition of thicker walls and darker pigmentation of the spores. The authors suggest that these sturdier spores were better able to tolerate the relatively harsher conditions on dry land (and, in some cases, in herbivore digestive tracts), where water conservation and resistance to ultraviolet radiation can be a great help. — PJH

    Mycol. Res. 111, 10.1016/j.mycres.2007.03.019 (2007).


    Outside Inside

    1. Stella Hurtley

    In macrophages that have been infected by HIV-1, the newly synthesized virions bud into an intracellular compartment, which has been thought to be derived from endosomes because it contains the endosomal membrane protein CD63. However, there currently is some controversy about the site of viral budding because a variety of viral components are directly targeted to the plasma membrane and because virus assembly has clearly been observed on the surface of infected T cells.

    Deneka et al. show that, although the budding compartment in macrophages appears at first glance to be intracellular, it is in fact still connected to the cell surface and can be accessed directly from the extracellular milieu. The authors identify several of the membrane proteins—three members of a protein family known as tetraspanins, CD81, CD9, and CD53—that define this unanticipated plasma membrane domain, and confirm that a similar compartment exists in uninfected cells. These membrane-delimited structures were accessible to two membrane-impermeant molecules (horse-radish peroxidase and ruthenium red) added to the external medium and also to antibodies (as long as the cells were kept at 4°C to prevent active uptake). These findings are consistent with recent work by Welsch et al. and by Jouvenet et al. that together support the notion that HIV normally buds from the plasma membrane during productive infection. — SMH

    J. Cell Biol. 177, 329 (2007); PLoS Pathog. 3, e36 (2007); PLoS Biol. 4, e435 (2006).


    A Material Difference for DFT

    1. Phil Szuromi

    The accuracy of density functional theory (DFT) calculations, which is limited by the approximate treatment of the exchange-correlation (XC) functional, can be tested for small systems by wave-function methods. In systems too large to easily apply such a test, especially those with strong electron correlations, it has often been hoped that the errors in total energies would cancel out when differences were evaluated. An example where this cancellation fails is the low-coverage adsorption of CO on close-packed surfaces of copper and platinum, for which DFT calculations favor the threefold hollow site over the experimentally determined “on top” site (binding to just one metal atom) by at least 0.4 eV. Hu et al. performed high-level quantum chemistry calculations on small metal clusters (copper and silver) to evaluate the XC energy error of DFT. The XC correction (the difference between the energy from DFT and that from the higher method) varies for different methods and continues to change as cluster size increases. However, because of the short-range nature of this error, the differences in the XC correction between different types of sites on the cluster converge to a constant at cluster sizes as small as ~20 atoms. By applying this correction to the DFT results, the authors obtained the correct on-top site preference for CO on copper, as well as the correct result for silver. This approach can also be applied to bulk systems and defects. — PDS

    Phys. Rev. Lett. 98, 176103 (2007).


    Through the Side Door

    1. Gilbert Chin

    The hydrolysis of peptide bonds is a common-place biochemical reaction and is catalyzed by innumerable proteases and peptidases, most of which have excruciatingly well-documented mechanisms. Because both of the reaction substrates are hydrophilic, it is not surprising that these enzymes are found and do function in aqueous compartments; a handful of proteases are, however, integral membrane proteins. Recent structural descriptions of the bacterial enzyme GlpG have placed the catalytic serine residue at a depth of about 10 Å beneath the surface of the lipid bilayer, which fits with the predicted location of the hydrolyzed peptide bonds in known intramembrane protease substrates.

    Baker et al. have mutated carefully chosen residues in GlpG and assessed the ability of the mutants to cleave the Drosophila protein Spitz, which is the substrate of the Drosophila intramembrane protease Rhomboid. They find that the substrate is likely to gain access, not by lifting the lidlike L1 loop on top of the active site, but by entering from within the lipid bilayer via a displacement of transmembrane helix 5, in a manner that is reminiscent of the translocon-mediated expulsion of newly synthesized membrane proteins. — GJC

    Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.0700814104 (2007).


    Water Lends a Hand

    1. Marc Lavine

    Although the global chirality of molecular aggregates is strongly influenced by the individual chirality of the building blocks, it is not generally a simple matter to predict one from the other. In a series of careful experiments, Johnson et al. uncover the subtle environmental factors that determine the helical handedness of rosette nanotubes assembled in solution from small organic heterocycles bearing a chiral side chain. The heterocycles (which are self-complementary toward hydrogen bonding) first form hexameric supermacrocycles, which in turn stack into a helical arrangement. Dissolution of a single enantiomer of this building block in methanol gives rise to one helical isomer, but addition of as little as 1% water to the solvent instead induces opposite helicity in the stacks. The authors show that the water-induced product is thermodynamically favored, but faces a larger kinetic barrier than its counterpart to formation in pure methanol (though aggregation in both senses appears to be accelerated in the absence of water). They further find that chiral inversion of the kinetic isomer in methanol can be catalyzed by the thermodynamic isomer. Inversion is also possible at an early stage by heating, though after 3 days the kinetic isomer becomes stereochemically locked, a result attributed in part to extensive solvation. — MSL

    J. Am. Chem. Soc. 129, 5735 (2007).

  6. STKE

    miRNAs Have Big Effects in the Heart

    1. Nancy Gough

    MicroRNAs (miRNAs) are important regulators of gene expression during development, through their ability to turn off the translation of targeted mRNAs. Two studies describe how miRNAs contribute to heart development and physiology {see also van Rooij et al., Science 316, 575 (2007)]. Yang et al. show that miR-1 abundance increases in patients with coronary heart disease and in rat models of cardiac infarction (heart attack), specifically in the ischemic area relative to the expression in the nonischemic area. Arrhythmias often occur after a heart attack and, in the rat model, delivery of an antisense oligonucleotide (which decreases the abundance of miR-1 in the myocardium) decreased postinfarct arrhythmias. Conversely, overexpression of miR-1 increased the occurrence of postinfarct arrhythmias and promoted arrhythmia in healthy hearts. The pathophysiology appeared to result from slowed conduction and depolarization of the heart, which were reversed by treatment with the miR-1 anti-sense oligonucleotide. Sequences complementary to miR-1 were present in the 3′-untranslated regions of the transcripts for the Kir2.1 subunit of the potassium channel, which is primarily responsible for setting the resting membrane potential, and for the connexin 43 gap junction protein. Indeed, these two proteins were less abundant in rats that had experienced myocardial infarction, and this drop was eliminated if the rats were treated with the antisense oligonucleotide to miR-1. To verify that these two proteins were responsible for the arrhythmias, each was knocked down by RNA interference, and this caused arrhythmias in ischemic hearts.

    Zhao et al. examined the role of miR-1-2 in heart development and found that homozygous knockout mice showed an increased occurrence of death due to ventricular septal defects, which may have been the result of increased abundance of the transcription factor Hand2 (a key regulator of cardiac morphogenesis). Mice that survived exhibited cardiac hyperplasia due to an increased number of postnatal cells undergoing cell division. These mice also exhibited cardiac arrhythmias, which appeared to be due to altered potassium channel abundance as a consequence of increased abundance of the transcription factor Irx5 (a repressor of the potassium channel gene Kcnd2). — NRG

    Nat. Med. 13, 486 (2007); Cell 129, 303 (2007).

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