12 results found
    1. Structural Biology and Molecular Biophysics

    Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating

    Gregory M Martin et al.
    Single-particle cryo-electron microscopy reveals the first subnanometer structure of ATP-sensitive potassium (KATP) channels, which provides insight into the structural mechanisms of channel assembly and gating.
    1. Structural Biology and Molecular Biophysics

    Mechanism of pharmacochaperoning in a mammalian KATP channel revealed by cryo-EM

    Gregory M Martin et al.
    Diverse KATP channel inhibitors occupy a common binding pocket and stabilize an interaction between Kir6.2 and SUR1 to allosterically control gating and promote the assembly and trafficking of nascent channels.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Anti-diabetic drug binding site in a mammalian KATP channel revealed by Cryo-EM

    Gregory M Martin et al.
    A structure of a pancreatic ATP-sensitive potassium channel complex at 3.63Å resolution obtained by cryo-electron microscopy reveals how a commonly used anti-diabetic drug interacts with and inhibits the channel to stimulate insulin secretion.
    1. Structural Biology and Molecular Biophysics

    Ion Channels: From ions to insulin

    Voula Kanelis
    Electron cryo-microscopy has revealed the three-dimensional structure of a potassium channel that has a central role in regulating the release of insulin from the pancreas.
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    1. Ecology

    Harbouring public good mutants within a pathogen population can increase both fitness and virulence

    Richard J Lindsay et al.
    Cooperation theory and a novel synthetic infection system provides a mechanistic understanding of why a seemingly successful disease management strategy can have devastating consequences for infected hosts.
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Molecular structure of human KATP in complex with ATP and ADP

    Kenneth Pak Kin Lee et al.
    MgADP binding to the high-affinity 'consensus' ATPase active site of SUR1 and remodeling of the L0-loop (lasso region) overrides tonic ATP inhibition of KATP channels.
    1. Developmental Biology
    2. Chromosomes and Gene Expression

    The Drosophila HNF4 nuclear receptor promotes glucose-stimulated insulin secretion and mitochondrial function in adults

    William E Barry, Carl S Thummel
    Drosophila HNF4 directs a developmental switch at the onset of adulthood that suppresses diabetes by promoting mitochondrial function and supporting glucose-stimulated insulin secretion.
    1. Neuroscience

    Early dysfunction and progressive degeneration of the subthalamic nucleus in mouse models of Huntington's disease

    Jeremy F Atherton et al.
    In mouse models of Huntington's disease, the subthalamic nucleus, which suppresses movements, also exhibits impaired glutamate homeostasis, NMDA receptor-dependent mitochondrial oxidant stress, firing disruption, and 30% neuronal loss.
    1. Cell Biology
    2. Developmental Biology

    Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway

    Barak Blum et al.
    Loss of mature β cell identity in diabetes can be prevented and rescued by small molecule inhibitors of the TGFβ pathway.
    1. Cell Biology
    2. Human Biology and Medicine

    Fusion pore regulation by cAMP/Epac2 controls cargo release during insulin exocytosis

    Alenka Guček et al.
    Live cell imaging shows that the cAMP-sensor Epac2, a target of major antidiabetic drugs, is central to fusion pore control during insulin granule exocytosis.

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