2,522 research outputs found
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Open and cut: allosteric motion and membrane fission by dynamin superfamily proteins.
Cells have evolved diverse protein-based machinery to reshape, cut, or fuse their membrane-delimited compartments. Dynamin superfamily proteins are principal components of this machinery and use their ability to hydrolyze GTP and to polymerize into helices and rings to achieve these goals. Nucleotide-binding, hydrolysis, and exchange reactions drive significant conformational changes across the dynamin family, and these changes alter the shape and stability of supramolecular dynamin oligomers, as well as the ability of dynamins to bind receptors and membranes. Mutations that interfere with the conformational repertoire of these enzymes, and hence with membrane fission, exist in several inherited human diseases. Here, we discuss insights from new x-ray crystal structures and cryo-EM reconstructions that have enabled us to infer some of the allosteric dynamics for these proteins. Together, these studies help us to understand how dynamins perform mechanical work, as well as how specific mutants of dynamin family proteins exhibit pathogenic properties
Going green: prospects for SME's to attain ISO 14001 and the challenges they face in the process
This research aimed to identify any common factors that have enabled and/or motivated SMEs to successfully implement ISO 14001 whilst the majority have not. It also identified what challenges and barriers SMEs face in doing so and how some have overcome these. The existing literature suggests that the majority of SMEs perceive their environmental impacts to be proportional to their size; have a poor understanding of environmental issues; have a poor awareness of environmental regulations; do that have the necessary expertise or leadership to address environmental issues and that SMEs with an environmental management system such as ISO 14001 are very much the minority. The main factors that influenced whether an SME had implemented ISO 14001 were: competitive advantage, regulatory compliance, supply chain pressures, leadership, expertise, resources and external support. This research used qualitative analysis of interviews with managers and directors from 8 SMEs with ISO 14001 and 4 without. All of the SMEs were based in the West Midlands or Staffordshire. Interviews were also conducted with 3 organisations offering support to businesses on environmental issues and with 1 large business who was engaging their suppliers (which included SMEs within this sample) on environmental issues. The research found that there were four main factors that enabled or motivated the SMEs to implement ISO 14001, these were: leadership, supply chain pressures, external support and SMEs' history and experience of accredited management systems. The main challenges that these business had to overcome and that prevented the other SMEs from achieving ISO 14001 were: achieving regulatory compliance, perceived financial cost, lack of perceived competitive advantage, access to relevant and affordable support and for those SMEs without ISO 14001 there was very little perceived external pressure or need for them to do so
Feedback between psychological science and policy in the context of same-sex couples
Psychological science informed recent policy changes granting increased rights for same-sex couples. Understanding that the link between science and policy goes both ways, how should policy inform the next generation of research concerning same-sex couples and sexual minority individuals? This article presents ways that psychological research influenced marriage policy and then puts forth suggestions for future research for the attention of scholars, funders, and policymakers. These include examinations of minority stress in the age of marriage equality; new stressors for same-sex couples including legal divorce; relationship expectations and experiences for emerging adults; and the potential impact of marriage equality for mixed-sex couples including a further challenge to strict gender roles in marriage. The article ends by acknowledging the need for continued application of research to emerging policy questions affecting same-sex couples and sexual minority individuals
The BAR Domain Superfamily: Membrane-Molding Macromolecules
Membrane-shaping proteins of the BAR domain superfamily are determinants of organelle biogenesis, membrane trafficking, cell division, and cell migration. An upsurge of research now reveals new principles of BAR domain-mediated membrane remodeling, enhancing our understanding of membrane curvature-mediated information processing
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Structural basis of mitochondrial receptor binding and constriction by DRP1.
Mitochondrial inheritance, genome maintenance and metabolic adaptation depend on organelle fission by dynamin-related protein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the paralogues mitochondrial dynamics proteins of 49 and 51 kDa (MID49 and MID51) and mitochondrial fission factor (MFF); however, the mechanisms by which these proteins recruit and regulate DRP1 are unknown. Here we present a cryo-electron microscopy structure of full-length human DRP1 co-assembled with MID49 and an analysis of structure- and disease-based mutations. We report that GTP induces a marked elongation and rotation of the GTPase domain, bundle-signalling element and connecting hinge loops of DRP1. In this conformation, a network of multivalent interactions promotes the polymerization of a linear DRP1 filament with MID49 or MID51. After co-assembly, GTP hydrolysis and exchange lead to MID receptor dissociation, filament shortening and curling of DRP1 oligomers into constricted and closed rings. Together, these views of full-length, receptor- and nucleotide-bound conformations reveal how DRP1 performs mechanical work through nucleotide-driven allostery
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