116 research outputs found

    Structure of a Complete ATP Synthase Dimer Reveals the Molecular Basis of Inner Mitochondrial Membrane Morphology

    Get PDF
    We determined the structure of a complete, dimeric F1Fo-ATP synthase from yeast Yarrowia lipolytica mitochondria by a combination of cryo-EM and X-ray crystallography. The final structure resolves 58 of the 60 dimer subunits. Horizontal helices of subunit a in Fo wrap around the c-ring rotor, and a total of six vertical helices assigned to subunits a, b, f, i, and 8 span the membrane. Subunit 8 (A6L in human) is an evolutionary derivative of the bacterial b subunit. On the lumenal membrane surface, subunit f establishes direct contact between the two monomers. Comparison with a cryo-EM map of the F1Fo monomer identifies subunits e and g at the lateral dimer interface. They do not form dimer contacts but enable dimer formation by inducing a strong membrane curvature of ∌100°. Our structure explains the structural basis of cristae formation in mitochondria, a landmark signature of eukaryotic cell morphology

    The ABC transporter MsbA adopts the wide inward-open conformation in E. coli cells

    Full text link
    Membrane proteins are currently investigated after detergent extraction from native cellular membranes and reconstitution into artificial liposomes or nanodiscs, thereby removing them from their physiological environment. However, to truly understand the biophysical properties of membrane proteins in a physiological environment, they must be investigated within living cells. Here, we used a spin-labeled nanobody to interrogate the conformational cycle of the ABC transporter MsbA by double electron-electron resonance. Unexpectedly, the wide inward-open conformation of MsbA, commonly considered a nonphysiological state, was found to be prominently populated in Escherichia coli cells. Molecular dynamics simulations revealed that extensive lateral portal opening is essential to provide access of its large natural substrate core lipid A to the binding cavity. Our work paves the way to investigate the conformational landscape of membrane proteins in cells

    The bowfin genome illuminates the developmental evolution of ray-finned fishes.

    Get PDF
    The bowfin (Amia calva) is a ray-finned fish that possesses a unique suite of ancestral and derived phenotypes, which are key to understanding vertebrate evolution. The phylogenetic position of bowfin as a representative of neopterygian fishes, its archetypical body plan and its unduplicated and slowly evolving genome make bowfin a central species for the genomic exploration of ray-finned fishes. Here we present a chromosome-level genome assembly for bowfin that enables gene-order analyses, settling long-debated neopterygian phylogenetic relationships. We examine chromatin accessibility and gene expression through bowfin development to investigate the evolution of immune, scale, respiratory and fin skeletal systems and identify hundreds of gene-regulatory loci conserved across vertebrates. These resources connect developmental evolution among bony fishes, further highlighting the bowfin's importance for illuminating vertebrate biology and diversity in the genomic era

    Creating a proof-of-concept climate service to assess future renewable energy mixes in Europe: an overview of the C3S ECEM project

    Get PDF
    The EU Copernicus Climate Change Service (C3S) European Climatic Energy Mixes (ECEM) has produced, in close collaboration with prospective users, a proof-of-concept climate service, or Demonstrator, designed to enable the energy industry and policy makers assess how well different energy supply mixes in Europe will meet demand, over different time horizons (from seasonal to long-term decadal planning), focusing on the role climate has on the mixes. The concept of C3S ECEM, its methodology and some results are presented here. The first part focuses on the construction of reference data sets for climate variables based on the ERA-Interim reanalysis. Subsequently, energy variables were created by transforming the bias-adjusted climate variables using a combination of statistical and physically-based models. A comprehensive set of measured energy supply and demand data was also collected, in order to assess the robustness of the conversion to energy variables. Climate and energy data have been produced both for the historical period (1979–2016) and for future projections (from 1981 to 2100, to also include a past reference period, but focusing on the 30 year period 2035–2065). The skill of current seasonal forecast systems for climate and energy variables has also been assessed. The C3S ECEM project was designed to provide ample opportunities for stakeholders to convey their needs and expectations, and assist in the development of a suitable Demonstrator. This is the tool that collects the output produced by C3S ECEM and presents it in a user-friendly and interactive format, and it therefore constitutes the essence of the C3S ECEM proof-of-concept climate service

    The price of mobility

    Get PDF
    This paper addresses the question concerning the price of geographic mobility in various labour market and migration scenarios. Pivotal points are expected mobility premiums which are sufficient to tip the scales in favour of moving to a geographically distinct location. These premiums are first derived within a theoretical model, accounting not only for location-specific amenity levels or labour market conditions, but also for heterogeneous personality traits and preferences. Derived hypotheses demonstrate that—in presence of heterogeneous psychic costs or adjustment capabilities—expected mobility premiums can remain distinctly positive even in an unemployment scenario. Furthermore, adjustment capabilities are to a large extent related to earlier mobility experiences, implying that labour mobility is partially learnable

    An Advanced Numerical Model of Gear Tooth Loading from Backlash and Profile Errors

    Get PDF
    This study demonstrates the early transient dynamic loading on teeth within a fixed-axis gear transmission arising from backlash and geometric manufacturing errors by utilizing a non-linear multi-body dynamics software model. Selection of the non-linear contact parameters such as the stiffness, force exponent, damping, and friction coefficients are presented for a practical transmission. Backlash between gear teeth which is essential to provide better lubrication on tooth surfaces and to eliminate interference is included as a defect and a necessary part of transmission design. Torsional vibration is shown to cause teeth separation and double-sided impacts in unloaded and lightly loaded gearing drives. Vibration and impact force distinctions between backlash and combinations of transmission errors are demonstrated under different initial velocities and load conditions. Additionally, the loading dynamics of a crank-slider mechanism with two-stage gear driving train is analyzed. The backlash and manufacturing errors in the first stage of the gear train are distinct from those of the second stage. By analyzing the signal at a location between the two stages, the mutually affected impact forces are observed from different gear pairs, a phenomenon not observed from single pair of gears
    • 

    corecore