BAX activation is initiated at a novel interaction site

BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha-helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB-BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.     

Impact origin of sediments at the Opportunity landing site on Mars

Mars Exploration Rover Opportunity discovered sediments with layered structures thought to be unique to aqueous deposition and with minerals attributed to evaporation of an acidic salty sea. Remarkable iron-rich spherules were ascribed to later groundwater alteration, and the inferred abundance of water reinforced optimism that Mars was once habitable. The layered structures, however, are not unique to water deposition, and the scenario encounters difficulties in accounting for highly soluble salts admixed with less soluble salts, the lack of clay minerals from acid-rock reactions, high sphericity and near-uniform sizes of the spherules and the absence of a basin boundary. Here we present a simple alternative explanation involving deposition from a ground-hugging turbulent flow of rock fragments, salts, sulphides, brines and ice produced by meteorite impact. Subsequent weathering by intergranular water films can account for all of the features observed without invoking shallow seas, lakes or near-surface aquifers. Layered sequences observed elsewhere on heavily cratered Mars and attributed to wind, water or volcanism may well have formed similarly. If so, the search for past life on Mars should be reassessed accordingly.     

STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane

As the sole Ca2+ entry mechanism in a variety of non-excitable cells, store-operated calcium (SOC) influx is important in Ca2+ signalling and many other cellular processes. A calcium-release-activated calcium (CRAC) channel in T lymphocytes is the best-characterized SOC influx channel and is essential to the immune response, sustained activity of CRAC channels being required for gene expression and proliferation. The molecular identity and the gating mechanism of SOC and CRAC channels have remained elusive. Previously we identified Stim and the mammalian homologue STIM1 as essential components of CRAC channel activation in Drosophila S2 cells and human T lymphocytes. Here we show that the expression of EF-hand mutants of Stim or STIM1 activates CRAC channels constitutively without changing Ca2+ store content. By immunofluorescence, EM localization and surface biotinylation we show that STIM1 migrates from endoplasmic-reticulum-like sites to the plasma membrane upon depletion of the Ca2+ store. We propose that STIM1 functions as the missing link between Ca2+ store depletion and SOC influx, serving as a Ca2+ sensor that translocates upon store depletion to the plasma membrane to activate CRAC channels.     

Birth of a metabolic gene cluster in yeast by adaptive gene relocation

Although most eukaryotic genomes lack operons, they contain some physical clusters of genes that are related in function despite being unrelated in sequence. How these clusters are formed during evolution is unknown. The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source. We show here that the DAL cluster was assembled, quite recently in evolutionary terms, through a set of genomic rearrangements that happened almost simultaneously. Six of the eight genes involved in allantoin degradation, which were previously scattered around the genome, became relocated to a single subtelomeric site in an ancestor of S. cerevisiae and Saccharomyces castellii. These genomic rearrangements coincided with a biochemical reorganization of the purine degradation pathway, which switched to importing allantoin instead of urate. This change eliminated urate oxidase, one of several oxygen-consuming enzymes that were lost by yeasts that can grow vigorously in anaerobic conditions. The DAL cluster is located in a domain of modified chromatin involving both H2A.Z histone exchange and Hst1-Sum1-mediated histone deacetylation, and it may be a coadapted gene complex formed by epistatic selection.     

Small mammals within riparian habitats of a regulated and unregulated arid land river

In northwestern Colorado, flow regulation on the Green River has created a transitional plant community that features encroachment by upland vegetation into cottonwood ( Populus fremontii )-dominated, riparian forest on topographically high floodplain sites and reduced cottonwood regeneration on low floodplain sites. To assess how these changes might have affected small mammal distributions, in 1994 and 1995 we live-trapped during periods surrounding spring flooding at 3 sites: above and below the confluence of the regulated Green River and at the ecologically similar, but unregulated, Yampa River (reference site). More species were captured at the most regulated site along the Green River above its confluence with the Yampa River. Within sites, more species were captured in riparian habitats than adjacent upland habitats. Despite river regulation-induced habitat changes, we did not detect changes in species distributions within low and high floodplain habitat for Peromyscus maniculatus or Microtus montanus , but changes may have occurred for Dipodomys ordii . The total effect of regulation-induced habitat change on small mammal populations may not be fully revealed until current, mature cottonwood forests disappear and associated woody debris decomposes.