609 research outputs found

    Synergistic recruitment of UbcH7~Ub and phosphorylated Ubl domain triggers parkin activation

    Get PDF
    The E3 ligase parkin ubiquitinates outer mitochondrial membrane proteins during oxidative stress and is linked to early-onset Parkinson’s disease. Parkin is autoinhibited but is activated by the kinase PINK1 that phosphorylates ubiquitin leading to parkin recruitment, and stimulates phosphorylation of parkin’s N-terminal ubiquitin-like (pUbl) domain. How these events alter the structure of parkin to allow recruitment of an E2~Ub conjugate and enhanced ubiquitination is an unresolved question. We present a model of an E2~Ub conjugate bound to the phosphoubiquitin-loaded C-terminus of parkin, derived from NMR chemical shift perturbation experiments. We show the UbcH7~Ub conjugate binds in the open state whereby conjugated ubiquitin binds to the RING1/IBR interface. Further, NMR and mass spectrometry experiments indicate the RING0/RING2 interface is re-modelled, remote from the E2 binding site, and this alters the reactivity of the RING2(Rcat) catalytic cysteine, needed for ubiquitin transfer. Our experiments provide evidence that parkin phosphorylation and E2~Ub recruitment act synergistically to enhance a weak interaction of the pUbl domain with the RING0 domain and rearrange the location of the RING2(Rcat) domain to drive parkin activity

    Longer wings for faster springs – wing length relates tospring phenology in a long-distanc e migrant across its range

    Get PDF
    In migratory birds, morphological adaptations for efficient migratory flight often oppose morphological adaptations for efficient behavior during resident periods. This includes adaptations in wing shape for either flying long distances or foraging in the vegetation and in climate-driven variation of body size. In addition, the timing of migratory flights and particularly the timely arrival at local breeding sites is crucial because fitness prospects depend on site-specific phenology. Thus, adaptations for efficient long-distance flights might be also related to conditions at destination areas. For an obligatory long-distance migrant, the common nightingale, we verified that wing length as the aerodynamically important trait, but not structural body size increased from the western to the eastern parts of the species range. In contrast with expectation from aerodynamic theory, however, wing length did not increase with increasing migration distances. Instead, wing length was associated with the phenology at breeding destinations, namely the speed of local spring green-up. We argue that longer wings are beneficial for adjusting migration speed to local conditions for birds breeding in habitats with fast spring green-up and thus short optimal arrival periods. We suggest that the speed of spring green-up at breeding sites is a fundamental variable determining the timing of migration that fine tune phenotypes in migrants across their range

    Origins of the Ambient Solar Wind: Implications for Space Weather

    Full text link
    The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

    Search for heavy resonances decaying into a vector boson and a Higgs boson in final states with charged leptons, neutrinos, and b quarks

    Get PDF
    Peer reviewe

    Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

    Get PDF
    Peer reviewe

    Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

    Get PDF
    Peer reviewe

    Measurement of the mass difference between top quark and antiquark in pp collisions at root s=8 TeV

    Get PDF
    Peer reviewe

    Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

    Get PDF
    Peer reviewe
    corecore